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1.
Statistical Evaluation of Trace Metals, TSH and T4 in Blood Serum of Thyroid Disease Patients in Comparison with Controls.
Hanif, S, Ilyas, A, Shah, MH
Biological trace element research. 2018;(1):58-70
Abstract
The present study is based on the measurement of concentrations of selected trace metals (Fe, Zn, Cu, Co, Mn, Ni, Cr, Cd and Pb) and thyroid hormones (TSH and T4) in blood serum of hypothyroid and hyperthyroid patients in comparison with healthy donors/controls in order to establish the imbalances of the trace metals in diseased subjects. The serum samples were digested in HNO3-HClO4 mixture and quantification of the metals was performed by flame atomic absorption spectrometry. Average levels of Fe, Ni, Cu, Cr, Pb and TSH were found to be significantly higher (p < 0.05) in the serum of hypothyroid patients compared with other donor categories, while mean concentrations of Mn, Cd and T4 were significantly elevated in the serum of hyperthyroid patients compared with other donor groups (p < 0.05). The correlation pattern of trace metals in the serum of patient groups revealed significantly different mutual associations compared with the controls. PCA and CA pointed out the interferences of the toxic metals with essential metals in the serum of both patient groups compared with the controls. Most of the metals exhibited noticeable disparities in their concentrations based on gender, food habits and tobacco use for all donor groups. Thus, the pathogenesis of thyroid diseases is significantly affecting the essential trace and toxic metals balance in both patients groups.
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2.
Iodine biokinetics and radioiodine exposure after recombinant human thyrotropin-assisted remnant ablation in comparison with thyroid hormone withdrawal.
Taïeb, D, Sebag, F, Farman-Ara, B, Portal, T, Baumstarck-Barrau, K, Fortanier, C, Bourrelly, M, Mancini, J, De Micco, C, Auquier, P, et al
The Journal of clinical endocrinology and metabolism. 2010;(7):3283-90
Abstract
CONTEXT A few prospective studies have evaluated the use of recombinant human TSH (rhTSH) for radioiodine remnant ablation. OBJECTIVE Our objective was to compare the effects of the both TSH regimens on iodine biokinetics in the thyroid remnant, dosimetry, and radiation protection. DESIGN We conducted a prospective randomized study. MATERIALS AND METHODS Eighty-eight patients were enrolled for radioiodine ablation to either the hypothyroid or rhTSH arms. A whole-body scan was performed at 48 and 144 h after therapy. Dose rates were assessed at 24, 48, and 144 h. Urinary samples were obtained during the first 48 h. Thyroglobulin was assessed before and after therapy. Iodine biokinetics in the remnants were calculated from gamma-count rates. Radiation-absorbed dose was calculated using OLINDA software. Exposure estimation was based on a validated model. RESULTS The effective half-life in the remnant thyroid tissue was significantly longer after rhTSH than during hypothyroidism (P = 0.01), whereas 48-h (131)I uptakes and residence times were similar. After therapy, thyroglobulin release (a marker of cell damage) was lower in the rhTSH arm. The mean total-body effective half-life and residence time were shorter in patients treated after rhTSH. Residence time was also lower for the colon and stomach. Absorbed dose estimates were lower in the rhTSH arm for the lower large intestine, breasts, ovaries, and the bone marrow. Dose rates at the time of discharge were lower in the rhTSH group with a reduction in cumulative radiation exposure to contact persons. CONCLUSIONS In comparison with thyroid hormone withdrawal, rhTSH is associated with longer remnant half-life of radioactive iodine while also reducing radiation exposure to the rest of the body and also to the general public who come in contact with such patients.
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3.
Chromosome translocation frequency after radioiodine thyroid remnant ablation: a comparison between recombinant human thyrotropin stimulation and prolonged levothyroxine withdrawal.
Frigo, A, Dardano, A, Danese, E, Davì, MV, Moghetti, P, Colato, C, Francia, G, Bernardi, F, Traino, C, Monzani, F, et al
The Journal of clinical endocrinology and metabolism. 2009;(9):3472-6
Abstract
BACKGROUND Thyroid remnant ablation of differentiated thyroid carcinoma (DTC) patients is traditionally performed after levothyroxine withdrawal. Recombinant human TSH (rhTSH) administration increases serum TSH levels without inducing hypothyroidism. AIM: The aim of the study was to investigate the frequency of chromosome translocations in DTC patients after the first (131)I therapeutic dose and compare the frequency of translocations between DTC patients off levothyroxine and those receiving rhTSH. PATIENTS AND METHODS A total of 20 DTC patients were randomly assigned to levothyroxine withdrawal [(30 d) group A; n=10, nine women; mean age 48.5+/- 19.2 yr] or rhTSH injections [(0.9 mg im per 2 consecutive days) group B; n=10, eight women; mean age 50.4+/- 18.8 yr] before undergoing (131)I activity (3.7 GBq). The frequency of translocations in peripheral lymphocytes was analyzed by tricolor fluorescence in situ hybridization with whole-chromosome-specific probes for chromosomes 1, 4, and 8. Lymphocytes were stained routinely (about 500 each time). RESULTS The two groups showed similar baseline translocation frequency. After (131)I administration, the total chromosomal translocation rate was significantly lower in group B than group A (P = 0.02). The frequency of translocations increased significantly in group A only (P = 0.01 vs. baseline). Rearrangement specifically involved chromosomes 4 and 8 (P = 0.02 vs. baseline). CONCLUSIONS Our preliminary data show that in hypothyroid status (131)I ablation therapy induces a higher translocation rate, especially in chromosomes 4 and 8. This finding, in agreement with previous dosimetric reports, suggests that whereas inducing a low extrathyroid exposure, rhTSH reduces the potential risk of chromosomal aberration associated with blood irradiation.
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4.
Surgery and radioablation therapy combined: introducing a 1-week-condensed procedure bonding total thyroidectomy and radioablation therapy with recombinant human TSH.
Emmanouilidis, N, Müller, JA, Jäger, MD, Kaaden, S, Helfritz, FA, Güner, Z, Kespohl, H, Knitsch, W, Knapp, WH, Klempnauer, J, et al
European journal of endocrinology. 2009;(5):763-9
Abstract
OBJECTIVE The objective of this study was to determine whether the use of recombinant human TSH (rhTSH) to stimulate radioiodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay. DESIGN Our aim was to compare the standard procedure of differentiated thyroid cancer treatment, which consists of thyroidectomy followed by 4 weeks of hypothyroidism and a conclusive ablative activity of (131)iodine, with a new shortened treatment in which l-thyroxine (T(4)) medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction in sick leave days overall without any reduction in safety or the efficacy of ablative therapy. METHODS Patients (n=25) were randomized either for surgery and rhTSH stimulation or surgery and l-T(4) abstinence before the first application of radioiodine. Ablation success was determined by neck ultrasound and serum thyroglobulin during follow-up. RhTSH receivers were monitored for an average of 635 days (s.d.+/-289) and patients in l-T(4) abstinence for an average of 624 days (s.d.+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick leave. RESULTS AND CONCLUSIONS Our shortened treatment proved to be equally efficacious and safe in comparison with the conventional therapy regimen. At the same time, it showed economic advantages through the reduction in average sick leave time from approximately 29 days (l-T(4) abstinence) down to approximately 6 days (rhTSH stimulation) as well as sustaining the patient's quality of life by the complete avoidance of hypothyroidism.
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5.
Comparison between remnant and red-marrow absorbed dose in thyroid cancer patients submitted to 131I ablative therapy after rh-TSH stimulation versus hypothyroidism induced by L-thyroxine withdrawal.
Vaiano, A, Claudio Traino, A, Boni, G, Grosso, M, Lazzeri, P, Colato, C, Davì, MV, Francia, G, Lazzeri, M, Mariani, G, et al
Nuclear medicine communications. 2007;(3):215-23
Abstract
OBJECTIVE In thyroidectomized patients, increased levels of thyroid stimulating hormone (TSH) are necessary to maximize I uptake. Traditionally, this has been achieved by withdrawing L-thyroxine (L-T4) for 4-6 weeks, inducing hypothyroidism in patients. The availability of a genetically engineered version of the recombinant human TSH (rh-TSH) provides an alternative tool to enhance the TSH serum level without inducing hypothyroidism. In this paper the I remnant and red-marrow doses calculated in differentiated thyroid cancer (DTC) patients pre-treated with rh-TSH are compared to those calculated in patients in hypothyroidism induced by L-T4 withdrawal. METHODS Forty-six DTC patients, submitted to I ablative therapy, were randomly divided in group A (pre-treated with rh-TSH) and group B (treated after L-T4 withdrawal for 30 days). The red-marrow absorbed dose per unit administered activity and the remnant cumulated activity per unit administered activity were calculated for both groups. RESULTS The red-marrow dose in 17 rh-TSH treated patients is 0.06+/-0.02 mGy.MBq; that in 14 hypothyroid patients is 0.09+/-0.03 mGy.MBq (two-tailed unpaired t-test P=0.003). The remnant cumulated activity per unit administered activity in 10 rh-TSH treated patients is 0.9+/-0.8 h; that calculated in 21 hypothyroid patients is 1.55+/-1.05 h (two-tailed unpaired t-test P=0.063). This last result is mainly due to the difference between the maximum uptake (U) in rh-TSH (U=0.01+/-0.01) and hypothyroid patients (U=0.03+/-0.02) (two-tailed unpaired t-test P=0.019). CONCLUSION The rh-TSH pre-treated patients seem to have a lower uptake compared to those in hypothyroidism induced by L-T4 withdrawal. On the other hand their red-marrow absorbed dose seems to be lower.
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6.
A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.
Pilli, T, Brianzoni, E, Capoccetti, F, Castagna, MG, Fattori, S, Poggiu, A, Rossi, G, Ferretti, F, Guarino, E, Burroni, L, et al
The Journal of clinical endocrinology and metabolism. 2007;(9):3542-6
Abstract
OBJECTIVE Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine ((131)I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq (131)I had a similar successful rate to 3700 MBq in patients prepared with rhTSH. DESIGN A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) (131)I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; (131)I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6-8 months later. RESULTS Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases. CONCLUSION Therapeutic (131)I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases.
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7.
Dosimetry of radioiodine therapy in patients with nodular goiter after pretreatment with a single, low dose of recombinant human thyroid-stimulating hormone.
Nieuwlaat, WA, Hermus, AR, Ross, HA, Buijs, WC, Edelbroek, MA, Bus, JW, Corstens, FH, Huysmans, DA
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2004;(4):626-33
Abstract
UNLABELLED A single, low dose of recombinant human thyroid-stimulating hormone (rhTSH) doubles 24-h RAIU and causes a more homogeneous distribution of radioiodine on thyroid scintigrams of patients with nodular goiter. Pretreatment with rhTSH allows the therapeutic dose of (131)I to be reduced by 50%-60% without compromising the result of thyroid volume reduction. The present study focused on the dosimetric aspects of therapy with a reduced dose of (131)I after pretreatment with rhTSH in patients with nodular goiter. METHODS Thirty-six patients were treated with (131)I to reduce thyroid volume. Nine patients were pretreated with a single dose of 0.01 mg of rhTSH, and 9 patients, with 0.03 mg of rhTSH. Two control groups of 9 patients, matched for thyroid weight and 24-h radioactive iodide uptake, were not pretreated with rhTSH. The therapeutic dose of (131)I was aimed at being sufficient to result in retention of 3.7 MBq of (131)I per gram of thyroid tissue at 24 h. Thyroid radioactivity after (131)I administration was measured every 24 h for 3 d and on days 7, 10, 14, 21, and 28. A model of iodine biokinetics was used to estimate absorbed doses in organs. Protein-bound (131)I activity was measured at 1, 2, 3, 7, and 10 d and at 2, 3, and 4 wk after (131)I therapy. RESULTS The administered activities were 1.5 times lower in the 0.01-mg rhTSH group and 1.9 times lower in the 0.03-mg rhTSH group than in the control groups. The absorbed dose in the thyroid was similar in the rhTSH-pretreated groups and in the control groups. In the organs of excretion (bladder) and uptake (stomach) of inorganic iodide, the absorbed doses were 2- to 3-fold lower in the pretreated groups than in the control groups. The effective dose equivalent outside the thyroid was considerably lower in the rhTSH-pretreated groups than in their respective control groups (1.6-fold in the 0.01-mg rhTSH group and 2.3-fold in the 0.03-mg rhTSH group). The time course of protein-bound (131)I activity in serum and the cumulated protein-bound (131)I activity in serum did not differ significantly between rhTSH-pretreated and control groups. CONCLUSION (131)I therapy after pretreatment with a single, low dose of rhTSH, with the dose reduced according to the rhTSH-induced increase in 24-h radioactive iodide uptake, caused lower radiation-absorbed doses in extrathyroidal organs and tissues, especially bladder and stomach, and no significant increase in the release of (131)I-labeled thyroid hormones into the circulation of patients with nodular goiter. Thus, this mode of therapy can be recommended, especially when the dose of radioiodine to be administered without rhTSH pretreatment is high.
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8.
Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal.
Pacini, F, Molinaro, E, Castagna, MG, Lippi, F, Ceccarelli, C, Agate, L, Elisei, R, Pinchera, A
The Journal of clinical endocrinology and metabolism. 2002;(9):4063-8
Abstract
The aim of the study was to assess whether stimulation by recombinant human TSH (rhTSH) may be used in patients with differentiated thyroid carcinoma for postsurgical ablation of thyroid remnants using a 30-mCi standard dose of (131)I during thyroid hormone therapy. The rate of ablation was prospectively compared in three groups of patients consecutively assigned to one of three treatment arms: in the first arm, patients (n = 50) were treated while hypothyroid (HYPO); in the second arm, patients (n = 42) were treated while HYPO and stimulated in addition with rhTSH (HYPO + rhTSH); in the third arm, patients (n = 70) were treated while euthyroid (EU) on thyroid hormone therapy and stimulated with rhTSH (EU + rhTSH). The outcome of thyroid ablation was assessed by conventional HYPO (131)I scan performed in HYPO state 6-10 months after ablation. Basal serum TSH was elevated in the HYPO and HYPO + rhTSH groups. In the EU + rhTSH group, basal serum TSH was 1.3 +/- 2.5 micro U/ml (range, <0.005-11.9 micro U/ml). After rhTSH, serum TSH significantly increased in the HYPO + rhTSH group and the EU + rhTSH group. Basal 24-h radioiodine thyroid bed uptake was 5.8 +/- 5.7% (range, 0.2-21%) and 5.4 +/- 5.7% (range, 0.2-26%) in the HYPO and HYPO + rhTSH groups, respectively. In the HYPO + rhTSH group, mean 24-h thyroid bed uptake rose to 9.4 +/- 9.5% (range, 0.2-46%) after rhTSH (P < 0.0001). The 24-h uptake after rhTSH in the EU + rhTSH group was 2.5 +/- 4.3% (range, 0.1-32%), significantly lower (P < 0.0001) than that found in the HYPO and HYPO + rhTSH groups. The rate of successful ablation was similar in the HYPO and HYPO + rhTSH groups (84% and 78.5%, respectively). A significantly lower rate of ablation (54%) was achieved in the EU + rhTSH group. Mean initial dose rate (the radiation dose delivered during the first hour after treatment) was significantly lower in the EU + rhTSH group (10.7 +/- 12.6 Gy/h) compared with the HYPO + rhTSH group (48.5 +/- 43 Gy/h) and the HYPO group (27.1 +/- 42.5 Gy/h). In conclusion, our study indicates that by using stimulation with rhTSH, a 30-mCi standard dose of radioiodine is not sufficient for a satisfactory thyroid ablation rate. Possible reasons for this failure may be the low 24-h radioiodine uptake, the low initial dose rate delivered to the residues, and the accelerated iodine clearance observed in EU patients. Possible alternatives for obtaining a satisfactory rate of thyroid ablation with rhTSH may consist of increasing the dose of radioiodine or using different protocols of rhTSH administration producing more prolonged thyroid cells stimulation.