Thyroxine Withdrawal Research Articles

Transiently impaired endothelial function during thyroid hormone withdrawal in differentiated thyroid cancer patients.

Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy. We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the day before thyroxine withdrawal(P1), the day before 131I administration(P2) and 4-6 weeks after RAI therapy(P3). A high-resolution ultrasound named flow-mediated dilation (FMD) was used to measure endothelial function of the patients. We analyzed the changes of FMD, thyroid function and lipids at three time points. FMD(P2) decreased significantly compared to FMD(P1) (P1vsP2, 8.05 ± 1.55vs 7.26 ± 1.50, p<0.001). There was no significant difference between FMD(P3) and FMD(P1) after restoring TSH (thyroid stimulating hormone) suppression therapy (P1 vs P3, 8.05 ± 1.55 vs 7.79 ± 1.38, p=0.146). Among all parameters, the change of low-density lipoprotein (ΔLDL) was the only factor correlated negatively with the change of FMD (ΔFMD) throughout the RAI therapy process (P1-2, r=-0.326, p=0.020; P2-3, r=-0.306, p=0.029). Endothelial function was transiently impaired in DTC patients at short-term hypothyroidism state during the RAI therapy, and immediately returned to the initial state after restoring TSH suppression therapy.

The "Non-Treated" Versus "LT3-Treated" Protocols of Short-Term Hypothyroidism Induction in Differentiated Thyroid Cancer: An Analysis of Hypothyroid Complications, Mood Disorders, and Quality of Life.

This study aimed to compare "non-treated" versus "levotriiodothyronine (LT3)-treated" protocols of short-term hypothyroidism induction prior to radioactive iodine (RAI) ablation therapy in differentiated thyroid cancer (DTC). A total of 120 DTC patients who had thyroxine withdrawal either via 4-week hypothyroidism induction (non-treated group, n=60) or 2-week administration and then 2-week withdrawal of LT3 (LT3-treated group, n=60) to induce hypothyroid state prior to RAI ablation after initial surgery were included. Complications related to hypothyroidism-induction, Beck Depression Inventory (BDI), Hospital Anxiety-Depression Scale (HADS), and SF-36 health-related quality of life (HRQoL) scores were recorded. In the non-treated group, transition from euthyroid to hypothyroid state was associated with significant increase in the likelihood of moderate-to-severe depression on BDI (p<0.001), presence of depression on HADS-D (p<0.001), presence of anxiety on HADS-A (6.7% during euthyroid state vs. 33.3% during hypothyroid state, p<0.001), and major syndrome on BPRS (0.0 vs. 10.0%, p=0.001) as well as significant decrease in all SF-36 HRQoL domain scores (p<0.001 for each). In conclusion, our findings indicate the likelihood of L3-treatment to enable a more favorable transition period from euthyroid to hypothyroid state without experiencing a deterioration in depression, anxiety, or HRQoL.

Prevalence of Transient Hypothyroidism in Children Diagnosed with Congenital Hypothyroidism between 2000 and 2016.

Newborn screening (NBS) for congenital hypothyroidism (CH) was introduced in Switzerland in 1977, which allowed for the preclinical, biochemical diagnosis. The aim of this study was to evaluate the prevalence of transient CH (tCH) in the canton of Zurich. In this analytical cohort study, all newborns born in the canton of Zurich, between the 1st of January 2000 and the 30st of June 2016, with a TSH value above 15 mU/L (whole blood) were included. There were 115 cases out of 247,918 babies born during the study period. However, 23 cases had to be excluded due to missing data. The definite diagnosis was made after a thyroxine withdrawal at 2 years of age. The total prevalence of confirmed CH and the female to male ratio (f/m) were 1:2695 and 2.17:1; for permanent CH (pCH), 1:3443 and 2.8:1; and for tCH, 1:12,396 and 1:1, respectively. The TSH value was significantly higher in pCH compared to tCH, at 130.3 (62.9-171.9) and 36.4 (26.5-53.3) (median and interquartile range), respectively (p < 0.001). The prevalences found for congenital hypothyroidism and its transient form are comparable to previous studies. TSH concentration at birth was predictive for the further course of the disease. Low birth weight correlated with a tCH, whereas low gestational age did not. The dominance of the female sex in congenital hypothyroidism is supported by a gender ratio of 2.17:1.

Low correlation between serum thyroglobulin and 131I radioiodine whole body scintigraphy: implication for postoperative disease surveillance in differentiated thyroid cancer

PurposeTo evaluate postoperative serum thyroglobulin (Tg) as a reliable tumor marker in low-risk differentiated thyroid cancer (DTC). MethodsTwo hundred and three patients met the selection criteria of >18 years old; who had undergone total or near total thyroidectomy; had a postoperative Tg, and had undergone 131I pre ablation whole body scan (PA-WBS). The primary endpoint was the correlation between Tg level and functional remnant thyroid tissues. Outcomes were categorized as concordant and discordant. Concordant results were positive Tg (>1 ng/ml) with positive PA-WBS or negative Tg (<1 ng/ml) with negative PA-WBS. Discordant results were negative Tg with a positive PA-WBS or positive Tg with a negative PA-WBS. To increase the sensitivity of Tg detection, we evaluated Tg in patients with high thyroid stimulating hormone (TSH) with serum level >30 mU/l on thyroxine withdrawal protocol. ResultsOne hundred ten patients (54.1%) had discordant results (p < 0.05) with positive PA-WBS and Tg <1 ng/ml, while 93 patients (45.9%) had concordant results. For concordant results, 88 patients had positive PA-WBS and Tg >1 ng/ml, and 5 patients had negative PA-WBS and Tg <1 ng/ml. There was no patient with Tg >1 ng/ml and negative PA-WBS. There were 74 patients with high TSH (>30 mU/l) on abstention (thyroxine withdrawal protocol). Twenty-four (32.5%) had discordant results (p < 0.001) and 50 (67.5%) had concordant results. ConclusionThere is low correlation between postoperative Tg and PA-WBS. The sole use of Tg as a serum biomarker for postoperative disease status may not be reliable.

Quality of life comparison in thyroxine hormone withdrawal versus triiodothyronine supplementation prior to radioiodine ablation in differentiated thyroid carcinoma: a prospective cohort study in the Indian population.

Thyroid withdrawal in preparation for radioiodine ablation (RIA) may have a profound impact on health-related quality of life (HRQL). Cost implications and scheduling limit the use of recombinant TSH and triiodothyronine (T3) with its shorter half-life is a conceptually attractive alternative. Prospective cohort study design with patients having withdrawal of thyroxine (n = 37) or T3 supplementation (n = 33). HRQL was assessed using EORTC QLQ-C30, QLQ-H&N35 and modified Billewicz questionnaires. Time interval to achieve optimal TSH levels (atleast30mIU/ml) prior to RIA was determined. With the exception of emotional domain (QLQ-C30 p = 0.045), LT3 supplementation did not confer significant benefit when compared to LT4 withdrawal. Target serum TSH levels was achieved in 95% of patients by week 4 post thyroidectomy. LT3 supplementation delivered equivocal benefit and therefore the alternate strategies to minimize the impact on HRQL of reduction in the duration of hypothyroidism in T4 withdrawal are suggested.

Impact of COVID-19 on thyroid cancer surgery and adjunct therapy.

COVID-19 has profoundly modified the way healthcare is delivered. Jordan imposed lockdown and restrictive policies between March 17 and May 20, 2020. We aimed to assess the impact of such measures on thyroid cancer treatment plans. In the specified period, 12 patients were scheduled for surgery. Since papillary carcinoma was the preoperative diagnosis in all cases, radioactive iodine ablation (RIA) therapy was also planned 3–4 weeks following surgery after withdrawing thyroxine and achieving a thyroid stimulating hormone (TSH) level > 30 mU/L. Thyroxine withdrawal is the routine method applied for RIA in Jordan as it is less costly compared to the rapid method of exogenous stimulation using recombinant TSH. All surgical procedures were performed without delay since all patients were asymptomatic per flu-like illness and came from a region of low COVID-19 prevalence. These included total thyroidectomy (n = 11), bilateral therapeutic central compartment neck dissection (n = 7), lateral compartment neck dissection (n = 5). However, the RIA treatment plan was altered considerably according to the period in which they were operated. 6 out of the 7 patients operated in March changed to the stimulated method of RIA at a considerable additional extra cost. The seventh patient and the April patient opt to delay RIA until after lockdown. The remaining cases (operated in May) followed the usual withdrawal method as restrictions were due to an end. The restrictive measures applied during COVID-19 did not affect the safe and timely delivery of surgical care. However, it added a financial and psychological burden to the entire cancer management plan.

Indirect assessment of the maximum empirical activity (250 mCi) with respect to dosimetry concepts in radioiodine therapy of metastatic differentiated thyroid cancer.

The development of reliable dosimetry models promotes the individualized therapy concept toward more success and less complications. This paper evaluates the traditional maximum empirical activity (250 mCi) and the benefit of joining two dosimetry approaches to optimize the therapeutic activity and radioiodine efficacy in metastatic differentiated thyroid cancer. Nineteen (12 females and seven males) patients with metastatic differentiated thyroid cancer were included in the present study. The mean age of the patients was 46±16 years. The mean height and weight were 1.67±0.11 m and 76±18 kg, respectively. Radioiodine treatment was given by recombinant human thyrotropin stimulation in seven patients, and thyroxine withdrawal was successful for the rest 12 patients. The mean thyroid-stimulating hormone value was 68±34 μIU/ml, and the mean thyroglobulin value was 408±356 ng/ml before therapy. After radiotracer administration, lesion-absorbed dose was calculated in addition to red marrow dose estimation via two different models. Total body and blood residence time was found to be 30±17 and 4.5±1.9 h, respectively. Red marrow absorbed dose was 0.535±0.262 Gy/100 mCi using the model accounts for red marrow dose surrogated by blood, and it was 0.398±0.212 Gy/100 mCi using a modified model with mean deviation of -24% (range: -19 to -31%). Red marrow absorbed dose was found to be 0.50±0.15 Gy/100 mCi in the levothyroxine withdrawal group, whereas it was 0.46±0.2 Gy/100 mCi for the patients who received recombinant human thyrotropin. Mean lesion-absorbed dose was 0.16±0.14 Gy/g/mCi. The speculated dose from 250 mCi iodine-131 was evaluated, as 65% of all lesions (n=27) would receive at least 100 Gy, whereas the percentage of bone lesions that would receive at least 100 Gy was only 55%. Upon to this study, red marrow dose varies with type of preparation as that of medication withdrawal cases was slightly higher than exogenous thyroid-stimulating hormone. Involvement of lesion and red marrow dose assessment through dosimetry protocol seems indeed valuable to optimize safe and effective activity compared with the conventional regime with 250 mCi as maximum empirical activity.

Evaluation of ablation of thyroid remnants with 1850 MBq iodine-131 in 67 patients with thyroid cancer.

Radioiodine remnant ablation (RRA) is used to destroy residual normal thyroid tissue after total thyroidectomy in differentiated thyroid carcinoma (DTC) patients. As 1850-MBq RRA is routinely performed at our facility, we evaluated the outcomes. Sixty-seven DTC patients without macroscopic residual lesions after total thyroidectomy were evaluated. Thyroglobulin (Tg) was measured 2-3 months before RRA with thyroxin administration (pretreatment); just before ablation after a 3-week iodine intake restriction with thyroxin withdrawal (THW) (N.=16) or recombinant human thyroid-stimulating hormone (rhTSH) stimulation (N.=51); and 3 months after RRA, after a 2-week iodine intake restriction and 3-week THW (N.=57) or rhTSH stimulation (N.=10). All patients received 131I (1850 MBq) treatment followed by 131I scintigraphy about 8 days later (8.18±0.91) and 131I scintigraphy (185 MBq) after the dosage 24 hours later 3months after RRA. Initial RRA goal was defined as negatively visible uptake in 131I thyroid bed (VUT) and a Tg level of <2 ng/mL 3 months after RRA. Rest 60 patients whose TSH levels were below 0.5 µIU/mL of all 67 patients were evaluated. Negatively VUT on 3 months after RRA was shown in 56 out of 60 patients (93.3%). Initial RRA goal was achieved in 21 (42.0%) of 50 patients, excluding 3 patients whose Tg levels 3 months after RRA were not measured and 7 patients with anti-Tg antibodies. Pretreatment Tg levels (P=0.0003) was significant predictive factor for Initial RRA goal on multivariate logistic regression analysis. RRA with 1850 MBq is effective by visual diagnosis, about 40% of all intermediate or high-risk DTC patients achieved initial RRA goals by both visual and Tg levels diagnosis.

Comparable Ablation Efficiency of 30 and 100 mCi of I-131 for Low to Intermediate Risk Thyroid Cancers Using Triple Negative Criteria.

There is controversy about ablation efficacy of low or high doses of radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi of RAI to achieve successful ablation in patients with low to intermediate risk DTC. This prospective cross sectional study was conducted from April 2013 to November 2015. Inclusion criteria were patients of either gender, 18 years or older, having low to intermediate risk papillary and follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant metastasis.Thirty-nine patients were administered 30 mCi of RAI while 61 patients were given 100 mCi. Informed consent was acquired from all patients and counseling was done by nuclear physicians regarding benefits and possible side effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after thyroxin withdrawal), these patients were followed up for stimulated TSH, thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies, negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve analysis was used to find diagnostic strength of baseline sTg to predict successful ablation. Successful ablation based upon triple negative criteria was 56% in the low dose and 57% in the high dose group (non-significant difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82% and 77% (again non-significant). The ROC curve revealed that a baseline sTg level ≤ 7.4 ng/ml had the highest diagnostic strength to predict successful ablation in all patients. We conclude that 30 mCi of RAI has similar ablation success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline sTg ≤ 7.4 ng/ml is a strong predictor of successful ablation in all patients. Low dose RAI is safer, more cost effective and more convenient for patients and healthcare providers.

Administration of Radioactive Iodine Therapy Within 1 Year After Total Thyroidectomy Does Not Affect Vocal Function.

The purpose of this study was to evaluate the impact of radioactive iodine therapy (RIT) on vocal function during the early follow-up period after total thyroidectomy (TT) using perceptive and objective measurements, questionnaires regarding subjective symptoms, and data on vocal function in a prospectively enrolled and serially followed thyroid cancer cohort. Of 212 patients who underwent TT and were screened between January and December 2010 at our hospital, 160 were included in the final analysis. Patients with the following histories were excluded: lateral neck dissection, organic vocal fold disease, external radiotherapy, and voice evaluation during thyroxine withdrawal. Patients were stratified into 3 groups: TT, TT with low-dose RIT (1.1-2.2 GBq), and TT with high-dose RIT (≥3.7 GBq). Voice evaluations were performed before surgery and at 1, 6, and 12 mo after TT. Vocal characteristics were altered after TT, including changes on the grade, roughness, and strain scale; increased amplitude perturbation; decreased fundamental frequency; narrowed pitch range; and global disturbances in subjective functional parameters on the voice handicap index. However, the degree of vocal changes among the 3 groups did not significantly differ within the 1-y postoperative follow-up period. According to the results of subgroup analyses of patients who demonstrated good voice outcomes after TT, there were no significant functional differences among the 3 groups. RIT at any dose does not affect vocal function within 1 y of TT.

Dynamic change of peripheral blood cell in patients with differentiated thyroid cancer before and after 131I treatment

Objective To evaluate the kinetics of peripheral blood cells in DTC patients before and after 131I treatment. Methods A total of 64 patients were divided into 2 groups with different therapeutic doses: high-dose group (3.70-5.55 GBq, n=24) and low-dose group (1.11 GBq, n=40). The WBC, neutrophils (NEUT), lymphocytes (LY), RBC and PLT were counted before operation, before 131I treatment, and on 3 d and 7 d after 131I treatment. One-way analysis of variance and two-sample t test were used to analyze the data. Results The counts of WBC and NEUT in both groups along with the LY in high-dose group varied significantly before, and on 3 d and 7 d after 131I treatment(WBC: high-dose group,(6.30±1.04),(8.86±2.07),(6.59±1.64) ×109/L; low-dose group,(6.65±1.48),(10.17±3.04),(7.17±1.57)×109/L; NEUT: high-dose group,(3.75±0.88),(6.42±1.91),(4.53±1.54)×109/L; low-dose group,(3.88±0.90),(7.12±2.77),(4.40±1.17)×109/L; LY: (2.11±0.67),(2.06±0.74),(1.59±0.49)×109/L;F values: 3.88 to 30.20, all P<0.05). The counts of WBC and NEUT in both groups were significantly higher on 3 d after 131I treatment than that before treatment (all P<0.05). The counts of WBC and NEUT in both groups along with the LY in high-dose group decreased significantly on 7 d compared to that on 3 d after 131I treatment (all P<0.05). The counts of LY in high-dose group also significantly decreased on 7 d after 131I treatment than before treatment(P<0.05). The counts of RBC before 131I treatment and LY on 7 d after 131I treatment were significantly different between the 2 groups(t=2.36, -4.30, both P<0.05). Compared with the counts before operation, LY, RBC and PLT were significantly higher (t values: from-4.92 to-2.45, all P<0.05) during hypothyroid state induced by thyroxine withdrawal before 131I treatment. Conclusions Short-term kinetics of WBC and NEUT present as an increase first followed by a decrease after 131I treatment; while LY of high-dose group presents as a gradually decrease. Hypothyroid state induced by levo-thyroxine withdrawal leads to increased counts of LY, RBC and PLT before 131I treatment. Key words: Thyroid neoplasms; Radiotherapy; Iodine radioisotopes; Blood cells

Effect of Short Term Thyroxin Withdrawal on Health Related Quality of Life in Differentiated Thyroid Carcinoma Patients

Background: We aimed to study the HRQL in patients with differentiated thyroid carcinoma (DTC) during hypothyroidism due to thyroxin withdrawal, which is induced routinely for iodine-131 (I-131) whole body scan and ablative treatment. Methods: Between September 2011 and March 2012, eligible patients with DTC who were referred to our institution for diagnostic or therapeutic radioiodine administration under hypothyroid conditions due to thyroid hormone withdrawal were asked to complete the psychological instruments rating their HRQL and psychological status. HRQL was studied using the Short Form (SF-36), Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), the total mood disturbance (TMD) score, Beck Depression Inventory (BDI).One hundred and forty three hypothyroid patients with DTC (F=101, M=42, age=58.7 yrs) who were also on low-iodine diet were included in this study. Hypothyroidism was induced by withdrawal of thyroxin replacement in all patients. Results: The results of SF-36 showed that the HRQL was significantly impaired in hypothyroid patients during withdrawal of thyroxin (physical component scale: 44.3 ± 9.5, mental component scale: 40.8 ± 10.2, p ≤ 0.001). Depression scores were in the normal or non-clinically relevant range: 4.1 ± 3.8 on the HADS-Depression and 8.3 ± 6.6 on the Beck Depression Index. However, the mean score of 28.8 ± 25.2 on the POMS TMD was within normal range. Conclusion: HRQL is impaired in hypothyroid patients with DTC during thyroxine withdrawal before I-131 whole body scan and radioiodine therapy.

Thyroid Doses and Skin Contaminations of Radioiodine

Radioiodine treatment, using iodine I-131, is one of the oldest clinical radionuclide therapy methods, and it is widely spread and currently used in the treatment of both thyreotoxicosis and thyroid cancer. The use of iodine may cause skin contaminations which may be a radiobiologic hazard and diagnostic problem. Reported hazards in the radiopharmaceutical production of I-131 for therapy purposes are rare, but they might cause therapeutic approaches due to radioiodine uptake in the thyroid and destruction of thyroid tissue (mean beta range, 0.8 mm). In this work a skin contamination causing a radioiodine thyroid uptake has been reported, together with thyroid cancer patients of receiving therapeutic doses of I-131 having skin contaminations from exudates. These skin contaminations were quantificated, dose calculations were performed based on serial gamma detector and quantitative whole body gamma imaging, including SPECT/CT. For serial gamma imaging, thyroid retention and whole clearance after oral administration, rhTSH stimulation and thyroxin withdrawal give different results and therefore serial uptake estimates and time-activity curves are essential parameters for dose evaluation. Similarly, accidental subcutaneous administration for calculating thyroid uptake requires serial measurement as well. In these patients, the skin contaminations did not cause any potential hazard to the environment nor to the hospital even though potential risks have been reported in the early days. Skin doses due to contaminations varied from 0.64 to 2.7 Gy. In the radiopharmaceutical production accidental skin contamination did not cause any harmful thyroid dose (80 mGy) due to rapid cleaning actions. Quantitative gamma imaging together with activity calibrated detectors is the prerequisite for appropriate dose calculations when routes of administration differ from clinical routine.

Practice trends in patients with persistent detectable thyroglobulin and negative diagnostic radioiodine whole body scans: a survey of American Thyroid Association members.

Management of patients with thyroglobulin (Tg)-positive/scan-negative thyroid cancer remains challenging. American Thyroid Association (ATA) guidelines recommend potential use of empiric (131)I therapy and various scanning modalities, but no standard for managing such cases exists. We surveyed ATA members to assess current practice in management of patients with Tg-positive/scan-negative disease. Members participated in a web-based survey of six case scenarios of Tg elevations but iodine scan negativity. A total of 288 ATA members (80% male) participated. Patient age, sex, and basal and stimulated Tg varied between the cases. Respondents were asked their opinion regarding empiric (131)I therapy use, including (131)I dose, use and duration of low-iodine diet, thyroxine withdrawal or recombinant human thyrotropin (rhTSH), and utilization of additional imaging (neck ultrasound (US) or positron emission tomography/computed tomography (PET/CT)) and reconsideration of (131)I therapy. Between 16% and 51% recommended initial use of empiric (131)I for the various scenarios. The majority chose a (131)I dose between 75 and 150 mCi, and 73% employed a low-iodine diet for two or more weeks. Preference between thyroxine withdrawal versus rhTSH was evenly split. More than 98% obtained a neck US if empiric (131)I was not given; 52-89% would proceed to PET/CT if US was negative. Only 44% used rhTSH stimulation in PET scan preparation. (131)I use was more common with stimulated Tg significantly >10 ng/mL. (131)I therapy was slightly more likely with PET-positive (56%) than PET-negative status (45%). Respondents were split regarding empiric (131)I if basal and stimulated Tg increased ≥150% over two years. Providers in North America less commonly utilized (131)I treatment than those from other areas. In the face of possible heterophilic antibody interference in the Tg assay, the majority did not recommend (131)I therapy. Empiric (131)I therapy is still utilized for patients with Tg-positive/scan-negative disease. Neck US is frequently used to further evaluate such cases as (18)FDG-PET/CT, albeit the latter is used somewhat less often. Use of (131)I therapy correlated with the degree of Tg elevation or development of Tg antibodies, and was recommended more commonly with PET-positive than PET-negative status in patients with lower Tg levels. (131)I was less commonly used by providers within North America.

Radioactive body burden measurements in (131)iodine therapy for differentiated thyroid cancer: effect of recombinant thyroid stimulating hormone in whole body (131)iodine clearance.

Protocols in the management of differentiated thyroid cancer, recommend adequate thyroid stimulating hormone (TSH) stimulation for radioactive 131I administrations, both for imaging and subsequent ablations. Commonly followed method is to achieve this by endogenous TSH stimulation by withdrawal of thyroxine. Numerous studies worldwide have reported comparable results with recombinant human thyroid stimulating hormone (rhTSH) intervention as conventional thyroxine hormone withdrawal. Radiation safety applications call for the need to understand radioactive 131I (RA131I) clearance pattern to estimate whole body doses when this new methodology is used in our institution. A study of radiation body burden estimation was undertaken in two groups of patients treated with RA131I; (a) one group of patients having thyroxine medication suspended for 5 weeks prior to therapy and (b) in the other group retaining thyroxine support with two rhTSH injections prior to therapy with RA131I. Sequential exposure rates at 1 m in the air were measured in these patients using a digital auto-ranging beta gamma survey instrument calibrated for measurement of exposure rates. The mean measured exposure rates at 1 m in μSv/h immediately after administration and at 24 h intervals until 3 days are used for calculating of effective ½ time of clearance of administered activity in both groups of patients, 81 patients in conventionally treated group (stop thyroxine) and 22 patients with rhTSH administration. The 131I activities ranged from 2.6 to 7.9 GBq. The mean administered 131I activities were 4.24 ± 0.95 GBq (n = 81) in “stop hormone” group and 5.11 ± 1.40 GBq (n = 22) in rhTSH group. The fall of radioactive body burden showed two clearance patterns within observed 72 h. Calculated T½eff values were 16.45 h (stop hormone group) 12.35 h (rhTSH group) for elapsed period of 48 h. Beyond 48 h post administration, clearance of RA131I takes place with T½eff> 20 h in both groups. Neck and stomach exposure rate measurements showed reduced uptakes in the neck for rhTSH patients compared with “stop thyroxine” group and results are comparable with other studies. Whole body clearance is faster for patients with rhTSH injection, resulting in less whole body absorbed doses, and dose to blood. These patients clear circulatory radioactivity faster, enabling them to be discharged sooner, thus reduce costs of the hospitalization. Reduction in background whole body count rate may improve the residual thyroid images in whole body scan. rhTSH provides TSH stimulation without withdrawal of thyroid hormone and hence can help patients to take up therapy without hormone deficient problems in the withdrawn period prior to RA131I therapy. This also will help in reducing the restriction time periods for patients to mix up with the general population and children.

Effect of experimental hyperthyroidism on the maximum acute exercise tolerance and neuromuscular performance in rats

Background Thyroid hormones regulate many physiologic functions such as energy and heat production, synthesis of proteins, and muscle contraction. Objective This study aims to demonstrate the mechanism by which hyperthyroidism affects neuromuscular performance and acute exercise tolerance and whether this effect is reversible or not after recovery in rats. Materials and methods Rats used in this study were divided into three groups, each containing 10 rats: (a) in the euthyroid group, rats were selected by measurement of serum FT3 (triiodothyronin), FT4 (tetraiodothyronine), and thyroid-stimulating hormone levels. (b) In the hyperthyroid group, hyperthyroidism was induced by Eltroxin in increasing doses, beginning from 50 μg to reach 200 μg/kg body weight daily by intragastric administration for 3 weeks. (c) In the recovery group, hyperthyroid rats are allowed to recover by exogenous thyroxine withdrawal for 25 days. After induction, body weight and the maximal swimming time were estimated, and then retro-orbital blood samples were collected for estimation of malondialdehyde and the total antioxidant capacity. Rats were then killed by cervical decapitation. Phrenic nerve diaphragm preparations were excised, connected to a four-channel oscillograph for measuring the strength of muscle contraction at the start of the experiment and after 30 min activity using both direct and indirect stimulation. Glucose uptake by the muscle during 30 min of activity and 30 min of recovery was estimated. Results The data show that hyperthyroidism induced by Eltroxin elevates serum malondialdehyde significantly when compared with the euthyroid group, whereas reduces total antioxidant capacity significantly. Hyperthyroidism was also associated with reduction of body weight, the maximal swimming time, the strength of skeletal muscle contraction induced by direct and indirect repetitive stimulation, and its glucose uptake. Conclusion Oxidative stress plays a critical role in the pathogenesis of hyperthyroidism, especially on skeletal muscle performance and exercise tolerance. This effect is reversible after restoration of the euthyroid state.

18-Fluorodeoxyglucose Positron Emission Tomography in the Early Diagnostic Workup of Differentiated Thyroid Cancer Patients with a Negative Post-Therapeutic Iodine Scan and Detectable Thyroglobulin

Surgery and high-dose radioactive iodine ((131)I) treatment are the cornerstones in the treatment of differentiated thyroid cancer. Patients without (131)I uptake on the post-therapeutic whole body scan (WBS), but with detectable thyroglobulin (Tg) during thyroxine withdrawal (Tg-off), are evaluated with an 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) for tumor localization within three months. The yield of (18)F-FDG-PET imaging and clinical usefulness of a Tg-off cutoff value to predict a positive scan were assessed. From 2002 to 2011, 52 patients with a negative WBS and concurrent detectable Tg-off were evaluated. Thirty-five PET scans were performed during initial treatment, 17 after recurrent disease. Thirty-two patients were on substitution therapy, 17 were evaluated with endogenous thyrotropin elevation, and 3 after recombinant human thyrotropin stimulation. To determine the Tg-off cutoff value, a receiver operating characteristic curve was used. Nine (17%) (18)F-FDG-PET scans were true positive, 3 (6%) false positive, 36 (69%) true negative, and 4 (8%) false negative (sensitivity 69%, specificity 92%). In 13%, a true-positive scan resulted in a change in the clinical management. The area under the receiver operating characteristic curve is 0.82 [CI 0.64-0.99] (p<0.01), and the Tg-off cutoff value is 38.00 ng/mL (sensitivity 67%, specificity 95%). Ninety percent of (18)F-FDG-PET true-positive patients had a Tg-off >2.00 ng/mL. An (18)F-FDG-PET within three months after a negative WBS with detectable Tg-off showed additional tumor localization in 17% of the patients, leading to a change in clinical management in 13%. A clinically useful Tg-off cutoff value was not found, but 90% of positive (18)F-FDG-PET scans occurred in patients with a Tg-off >2.00 ng/mL.

The value of recombinant human TSH-aided 131 I treatment in differentiated thyroid carcinoma patients

Objective To evaluate the efficacy and safety of recombinant human TSH(rhTSH)-aided 131I treatment for DTC.Methods A total of 144 patients with DTC who underwent total or near total thyroidectomy were retrospectively analyzed.The rhTSH-aided 131I treatment of 3.7 GBq was performed in 72 cases (Group Ⅰ:euthyroid).Another 72 cases received radioiodine ablation treatment of 3.7 GBq after 4 to 6 weeks of thyroxine withdrawal (Group Ⅱ:hypothyroidism).Serum endogenous TSH,FT3,FT4 and Tg were measured.The life qualities of both groups were observed,such as intolerance to cold,weight gain,constipation,motor retardation,skin dryness,periorbital edema and bone pain.Absence of visible uptake or uptake rate less than 1％ was taken as complete ablation.The efficacy of 131I treatment was evaluated.The life quality of both groups was evaluated byx2 test,and the effect of 131I treatment was analyzed by t test.Results Serum TSH was effectively improved in both groups before 131I treatment.In group Ⅰ,TSH was higher than that of group Ⅱ ((141.26 ± 27.30) mU/L vs (70.57 ± 51.13) mU/L; t =2.435,P ＜0.05),and FT3,FT4 were not significantly different before or after the injection of rhTSH.Tg was well stimulated in both groups with no statistical difference.Group Ⅱ exhibited more side effects,which included intolerance to cold 80.56％(58/72),weight gain 86.11％ (62/72),constipation 15.28％ (11/72),motor retardation 22.22％ (16/72),skin dryness 56.94％ (41/72),bone pain 2.78％ (2/72),and no periorbital edema was found.Group Ⅰ had a higher quality of life than group Ⅱ,only few side effects were observed including dizziness and nausea 2.78％ (2/72),bone pain 2.78％ (2/72),and transient tachycardia 1.39％ (1/72).The effect of 131I treatment was evaluated by whole body scans with a diagnostic dose of 131I.The complete ablation rate was 70.83％ (51/72) in group I and 66.67％ (48/72) in group Ⅱ(x2 =0.58,P ＞ 0.05).Conclusion The rhTSH-aided 131I treatment can effectively improve patients' life quality and acquire satisfactory 131I ablation efficacy. Key words: Thyroid neoplasms ; Thyrotropin ; Recombinant; Radiotherapy; Iodine radioisotopes

Evaluation of whole-body scan, stimulated thyroglobulin after thyroxine withdrawal vs recombinant TSH administration according to the risk groups of tumor recurrence

Evaluation of whole-body scan, stimulated thyroglobulin after thyroxine withdrawal vs recombinant TSH administration according to the risk groups of tumor recurrence

In Thyroidectomized Patients with Thyroid Cancer, a Serum Thyrotropin of 30 μU/mL After Thyroxine Withdrawal Is Not Always Adequate for Detecting an Elevated Stimulated Serum Thyroglobulin

The thyrotropin (TSH) level or duration of thyroid hormone withdrawal (THW) required to detect stimulated thyroglobulin (Tg) in differentiated thyroid cancer (DTC) monitoring is unknown. The objective of this study was to evaluate the TSH cutoff of >30 μU/mL as a means to detect stimulated Tg ≥2 ng/mL after THW (THW-Tg≥2), and sensitivity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire for detecting hypothyroid symptoms. This was a prospective longitudinal cohort study done at a tertiary academic medical center. Forty-seven patients with DTC undergoing their first Tg stimulation or after previously abnormal Tg stimulation had weekly measurements of TSH and Tg during the 4 weeks THW, and repeated questionnaire assessments. TSH did not reach a plateau in any patient, and in those whose Tg did not remain undetectable, Tg continued to rise. Seventy-five percent of patients had an undetectable Tg <0.2 ng/mL at baseline (95% were <0.5 mg/mL) with 16% remaining undetectable throughout THW. The majority of patients (72.7% and 97.8%) achieved TSH >30 μU/mL by 3 and 4 weeks THW, respectively. Of the 15 patients with maximum stimulated THW-Tg≥2, 38% were detected before the minimal TSH >30 μU/mL cutoff. At 2 weeks THW, 3 had a TSH>30 μU/mL, and none of them had Tg ≥2 ng/mL. At 3 weeks THW, 11 had a TSH >30 μU/mL, and 64% of them had Tg ≥2 ng/mL. Only 60% were detected at 3-week THW regardless of their TSH level. Eighty-six percent were detected by TSH 60-<80 μU/mL. Conversely, all patients whose serum Tg was <0.2 ng/mL when their serum TSH was >20 μU/mL did not achieve a THW-Tg≥2. The minimal TSH cutoff of >30 μU/mL was inadequate to detect many patients with final stimulated THW-Tg≥2 during complete THW. TSH >80-100 μU/mL was a better cutoff, achieved in only 53% after 4-week THW. Conversely, we propose a preliminary THW-stopping rule for ending THW early in selected patients. In patients with a Tg <0.2 ng/mL when TSH >20 μU/mL, all had a final stimulated Tg ≤2 ng/mL, potentially saving qualifying patients 40% of THW duration compared to 4-week THW. FACIT-F correlated with TSH, but was not sensitive to detect mild hypothyroidism.