Thyroid Diseases: Luster M

Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E, Anonymous00011. · Department of Nuclear Medicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. · Eur J Nucl Med Mol Imaging. · Pubmed #18670773 No free full text.

Abstract: INTRODUCTION: The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine ((131)I) activities. DISCUSSION: For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with (131)I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.

Lassmann M, Hänscheid H, Chiesa C, Hindorf C, Flux G, Luster M, Anonymous00045. · Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany. · Eur J Nucl Med Mol Imaging. · Pubmed #18491092 No free full text.

Abstract: INTRODUCTION: The purpose of the EANM Dosimetry Committee Series on "Standard Operational Procedures for Pre-therapeutic Dosimetry" (SOP) is to provide advice to scientists and clinicians on how to perform pre-therapeutic and/or therapeutic patient-specific absorbed dose assessments. MATERIAL AND METHODS: This particular SOP gives advice on how to tailor the therapeutic activity to be administered for systemic treatment of differentiated thyroid cancer (DTC) such that the absorbed dose to the blood does not exceed 2 Gy (a widely accepted limit for bone marrow toxicity). The methodology of blood-based dosimetry has been developed in the 1960s and refined in a series of international multi-centre trials in the framework of the introduction of new diagnostic and therapeutic tools, e.g. recombinant human thyroid-stimulating hormone in the management of DTC. CONCLUSION: The intention is to guide the user through a series of measurements and calculations which the authors consider to be the best and most reproducible way at present.

Verburg FA, Dietlein M, Lassmann M, Luster M, Reiners C. · No affiliation provided · Eur J Nucl Med Mol Imaging. · Pubmed #19050874 No free full text.

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Haugen BR, Cooper DS, Emerson CH, Luster M, Maciel RM, Biscolla RP, Mazzaferri EL, Medeiros-Neto G, Reiners C, Robbins RJ, Robinson BG, Schlumberger M, Yamashita S, Pacini F. · No affiliation provided · Thyroid. · Pubmed #18630995 links to  free full text

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Reiners C, Dietlein M, Luster M. · Department of Nuclear Medicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. · Best Pract Res Clin Endocrinol Metab. · Pubmed #19041827 No free full text.

Abstract: Post-surgical ablative iodine-131 therapy is recommended for all differentiated thyroid cancer primary tumors>1 cm in diameter. Regarding smaller primary tumors, 131I ablation may be helpful in special cases: tumor close to the thyroid capsule, previous percutaneous radiation to the neck, familial occurrence of thyroid cancer, tumor diameter 5-10 mm, and unfavorable histological variants. In this context, the patient's preferences for safety should be considered. In most centers, standard fixed activities of 1-3 GBq are used for 131I ablation. Preparation for the procedure with such activities requires a low-iodine diet for 2-3 weeks and stimulation of thyroid stimulating hormone (TSH) by withholding of thyroid hormone for 3 weeks following thyroidectomy or by use of recombinant human TSH. The advantages of recombinant TSH are avoidance of hypothyroid morbidity and consequently a better quality of life, as well as a lower radiation dose to extra-thyroidal compartments. To treat metastastic differentiated thyroid cancer, higher activities of radio-iodine (in the range 4-11 GBq) are necessary; if possible, individual dosimetry is recommended. The standard approach to preparation for 131I therapy in patients with metastases is endogenous hypothyroidism after thyroid hormone withdrawal.

Reiners C, Dietlein M, Luster M. · Klinik und Poliklinik für Nuklearmedizin, Universität Würzburg. · Dtsch Med Wochenschr. · Pubmed #18924056 No free full text.

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Luster M, Lassmann M, Freudenberg LS, Reiners C. · Department of Nuclear Medicine, University of Würzburg, Germany. · Hormones (Athens). · Pubmed #18055418 links to  free full text

Abstract: Thyroid cancer, although very rare in childhood, represents the most common pediatric endocrine neoplasia. The low incidence and the resulting limited availability of prospective, randomized trials lead to a lack of evidence- based recommendations for treatment strategies. Total thyroidectomy and lymphadenectomy, when indicated, followed by ablative radioiodine treatment, are considered the cornerstones of initial patient management which decrease the risk of relapse. On the other hand, less aggressive treatment modalities should also be aimed at due to the high life expectancy of this special patient group and the potential impairment of the quality of life. These considerations have led to individualized "tailored" therapeutic approaches based on prior risk stratification. This article mainly deals with novel nuclear medicine concepts for dosing regimens in radioiodine therapy.

Oyen WJ, Bodei L, Giammarile F, Maecke HR, Tennvall J, Luster M, Brans B. · Therapy Committee of the European Association of Nuclear Medicine, Hollandstrasse 14 / Mezzanine, A-1020 Vienna, Austria. · Ann Oncol. · Pubmed #17434893 links to  free full text

Abstract: In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored.

Brans B, Bodei L, Giammarile F, Linden O, Luster M, Oyen WJ, Tennvall J. · Department of Nuclear Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. · Eur J Nucl Med Mol Imaging. · Pubmed #17268773 links to  free full text

Abstract: INTRODUCTION: Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy. REVIEW: This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce. DEVELOPMENTS: In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally.

Luster M, Lippi F, Jarzab B, Perros P, Lassmann M, Reiners C, Pacini F. · Department of Nuclear Medicine, University of Würzburg, Josef-Schneider-Str.2,97080 Würzburg, Germany. · Endocr Relat Cancer. · Pubmed #15788638 links to  free full text

Abstract: Traditionally, withdrawal of thyroid hormone has been used to attain the increase in serum TSH concentrations that are believed to optimize the trapping and retention of radioiodine for diagnostic procedures, thyroid remnant ablation and treatment of patients with differentiated thyroid cancer (DTC). However, withdrawal frequently causes clinical hypothyroidism, with resultant cognitive impairment, emotional dysfunction, physical discomfort, health risks in patients who are elderly, frail or have concomitant illness, and impaired quality of life and ability to work. Recombinant human TSH (rhTSH) was developed to provide TSH stimulation without withdrawal of thyroid hormone and the associated morbidity. rhTSH has been approved as an adjunct for diagnostic procedures in patients with DTC, but is currently an experimental aid in thyroid remnant ablation and the treatment of thyroid tumours. In the period 1997-2004, nearly 30 medical centres worldwide have reported on almost 400 patients with DTC who were given rhTSH in preparation for radioiodine ablation of thyroid remnants or treatment of local tumours of metastatic disease. We have analysed and summarized the findings reported in this literature. Ablation aided by the standard course of rhTSH, two consecutive daily injections of 0.9 mg, had success rates better than 84% in 90 patients given radioiodine activities in excess of 4000 MBq. However, when 1110 MBq was administered, success rates were 81.2% in 16 patients given the standard course of rhTSH and 4-day withdrawal of thyroid hormone around the time of radioiodine administration in one study, but 54% in 70 patients in another study. rhTSH-aided treatment of persistent or recurrent local or metastatic cancer, or both, with from one to six courses of radioiodine 1000-19055 MBq, achieved 2% complete remission, 36% partial response and 27% disease stabilization rates, for a 65% clinical benefit rate, in 115 primarily elderly, late-stage patients for whom responses were reported. Twelve of these patients died as a result of progressive disease or were discharged from hospital into hospice care. Generally, rhTSH was very well tolerated. However, in a minority of patients with central nervous system, spinal or bone metastases, or bulky thyroid remnant or neck lesions with or without poor pulmonary reserve, administration of rhTSH, like thyroid hormone withdrawal, was found to stimulate expansion of the tumour, with ensuing compression of key anatomical structures and neurological, respiratory or other clinical complications. The rapid onset, response to glucocorticoids and radiological findings of peritumoural oedema or, less commonly, haemorrhage in the published cases, strongly suggest that the tumour expansion was the result of swelling rather than growth. As in the case of thyroid hormone withdrawal, special attention and glucocorticoid premedication are thus warranted when rhTSH is given to patients known or suspected to have the above characteristics. Dosimetric data suggest that whole-body and whole-blood radioiodine clearance may be faster in euthyroid patients after administration of rhTSH. In theory, the faster clearance could allow, or demand, increased radioiodine activities when rhTSH is used, but clinical data to date suggest that this may be unnecessary. The faster clearance also might result in safety or convenience benefits with the use of rhTSH, such as decreased exposure of extrathyroid areas to radiation, and shorter hospital stays. In conclusion, in preliminary results from open-label studies, both rhTSH-aided tumour ablation and treatment have been well tolerated and have shown efficacy in substantial proportions of patients. rhTSH-aided ablation merits further study. rhTSH-aided treatment may be preferred in patients who are at greater risk of hypothyroid complications from withdrawal of thyroid hormone or are unable to produce sufficient endogenous TSH, and warrants additional investigation in younger patients at earlier stages of thyroid cancer.

Reiners C, Luster M, Lassmann M. · Nuclear Medicine Clinic, University of Würzburg, Germany. · J Endocrinol Invest. · Pubmed #10727001 No free full text.

Abstract: Whole-body scanning (WBS) with iodine-131 (I-131) is currently used together with serum thyroglobulin (Tg) measurement in the diagnostic follow-up of well-differentiated thyroid carcinoma. One of the main disadvantages of I-131 WBS is its requirement of repeated weeks-long withdrawal of thyroid hormone suppression therapy (THST) to raise endogenous thyroid-stimulating hormone (TSH) production. This results in hypothyroidism and associated abnormalities, discomfort and morbidity. Recently, however, a series of multicentre clinical studies established the efficacy, safety, non-antigenicity, and quality of life benefits of recombinant human TSH (rhTSH, Thyrogen, thyrotropin alfa, Genzyme Corporation, Cambridge, MA, USA) in promoting radioiodine uptake and permitting sensitive I-131 WBS in patients on THST after initial therapy of well-differentiated thyroid cancer. Thus in everyday practice, rhTSH administration may in many cases supersede THST withdrawal as a preparative method for I-131 imaging. With the use of rhTSH, as whenever I-131 WBS is performed, useful and accurate imaging requires meticulous attention to good scanning practices. These include use of appropriate equipment, proper timing, sufficient scanning time, vigilance against artifacts and iodine contamination, and consideration of additional imaging in the case of ambiguous 48-hour scans. Whole-body retention of I-131 is approximately 50% greater during hypothyroidism after THST withdrawal than during euthyroidism on THST and rhTSH. Therefore, it is important to use an adequate diagnostic activity of > or =4 mCi (148 MBq) to compensate for the faster radioiodine clearance in the euthyroid state permitted by rhTSH administration. Ongoing dosimetric research eventually may provide more specific guidance regarding radioiodine activities for diagnostic, and, particularly, therapeutic purposes, with the use of rhTSH.

Schroeder PR, Haugen BR, Pacini F, Reiners C, Schlumberger M, Sherman SI, Cooper DS, Schuff KG, Braverman LE, Skarulis MC, Davies TF, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Weintraub BD, Ridgway EC, Ladenson PW. · Johns Hopkins Medical Institutions, Division of Endocrinology and Metabolism, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA. · J Clin Endocrinol Metab. · Pubmed #16394083 links to  free full text

Abstract: CONTEXT: Thyroid carcinoma requires lifelong monitoring with serum thyroglobulin, radioactive iodine whole body scanning, and other imaging modalities. Levothyroxine (L-T4) withdrawal for thyroglobulin measurement and whole body scanning increases these tests' sensitivities but causes hypothyroidism. Recombinant human TSH (rhTSH) enables testing without L-T4 withdrawal. OBJECTIVE: Our objective was to examine the impact of short-term hypothyroidism on the health-related quality of life (HRQOL) of patients after rhTSH vs. L-T4 withdrawal. DESIGN, SETTING, AND PATIENTS: In this multicenter study, the SF-36 Health Survey was administered to 228 patients at three time points: on L-T4, after rhTSH, and after L-T4 withdrawal. Interventions: Interventions included administration of rhTSH on L-T4 and withdrawal from thyroid hormone. MAIN OUTCOME MEASURES: Mean SF-36 scores were compared during the two interventions and with the U.S. general population and patients with heart failure, depression, and migraine headache. RESULTS: Patients had SF-36 scores at or above the norm for the general U.S. population in six of eight domains at baseline on L-T4 and in seven of eight domains after rhTSH. Patients' scores declined significantly in all eight domains after L-T4 withdrawal when compared with the other two periods (P < 0.0001). Patients' HRQOL scores while on L-T4 and after rhTSH were at or above those for patients with heart failure, depression, and migraine in all eight domains. After L-T4 withdrawal, patients' HRQOL scores were significantly below congestive heart failure, depression, and migraine headache norms in six, three, and six of the eight domains, respectively. CONCLUSIONS: Short-term hypothyroidism after L-T4 withdrawal is associated with a significant decline in quality of life that is abrogated by rhTSH use.

Lassmann M, Luster M, Hänscheid H, Reiners C. · Klinik und Poliklinik für Nuklearmedizin der Universität Würzburg, Würzburg, Germany. · J Nucl Med. · Pubmed #15073258 links to  free full text

Abstract: Recent publications described many discrepant findings about thyroid "stunning" after the administration of (131)I diagnostic activities to patients with differentiated thyroid carcinoma. Stunning may play a major role in reducing the therapeutic efficacy of high (131)I activities given for ablation therapy. METHODS: Participation in a multicenter study to investigate differences in iodine biokinetics in the hypothyroid state and after the application of recombinant human thyroid-stimulating hormone enabled us to study quantitative changes in thyroid iodine biokinetics after the administration of 74 MBq of (131)I twice within 6 wk and an ablation activity of 3-4 GBq 7-12 d after the second diagnostic administration of (131)I in 6 patients. RESULTS: The uptake and half-life of the first 74 MBq of (131)I were significantly reduced to a mean of 44% and a mean of 51%, respectively, after the second diagnostic administration and further reduced to a mean of 40% and a mean of 30%, respectively, during ablation therapy. The residence times were reduced to 25% in the second dosimetric assessment and to 10% during therapy compared with the value in the first assessment. For one patient, an estimated absorbed dose as high as 38 Gy was found in the first diagnostic study. The mean dose for all patients after the first assessment was 15 Gy; after each further assessment, the dose was reduced according to the decrease in residence time. CONCLUSION: This study shows a severe impact of 74 MBq of (131)I on the biokinetics of thyroid remnants during subsequent radioiodine therapy.

Luster M, Sherman SI, Skarulis MC, Reynolds JR, Lassmann M, Hänscheid H, Reiners C. · Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany. · Eur J Nucl Med Mol Imaging. · Pubmed #12856155 No free full text.

Abstract: Iodine kinetics were studied in patients with differentiated thyroid cancer while euthyroid under exogenous thyroid stimulating hormone (TSH) and while hypothyroid to detect differences in radioiodine uptake, distribution and elimination. Nine patients with total or near-total thyroidectomy on thyroid hormone suppressive therapy received two or three daily doses of 0.9 mg recombinant human TSH (rhTSH) followed by administration of a diagnostic activity of 2 mCi (74 MBq) iodine-131. After the biokinetics assessments had been performed, patients stopped taking thyroid hormones to become hypothyroid. A second 2 mCi (74 MBq) diagnostic activity of 131I was administered, followed by a second set of biokinetics assessments. One week later the patients underwent remnant ablation with a therapeutic activity of 131I. A comparison of the 131I kinetics in the patients while euthyroid and while hypothyroid showed major differences in the doses to the remnant as well as in residence times and radiation exposure to the blood. In the first diagnostic assessment the remnant dose was higher in eight of the nine patients and clearance of the activity from the blood was faster in all of them. The data from this study suggest that radioiodine administration is potent and safe when administered to euthyroid patients following rhTSH administration. Enhanced residence time in the remnant and decreased radiation exposure to the blood were noted when patients were euthyroid compared to when they were rendered hypothyroid. However, all patients received diagnostic activities in the same order: first while euthyroid, followed by hypothyroidism. It is quite possible that "stunning" from the radioiodine administered in the initial uptake study inhibited the subsequent uptake of radioiodine by the remnant lesions in the second uptake study.

Luster M, Lassmann M, Haenscheid H, Michalowski U, Incerti C, Reiners C. · Department of Nuclear Medicine, University of Wuerzburg, Germany. · J Clin Endocrinol Metab. · Pubmed #11061516 links to  free full text

Abstract: The use of 131I for radioablative therapy in patients with differentiated thyroid cancer (DTC) requires a sufficient serum concentration of TSH for efficient thyroid tissue uptake of iodine. We describe the use of recombinant human TSH (rhTSH) in conjunction with ablative radioiodine therapy (RIT) in 11 patients (16 total treatments) with advanced and/or recurrent DTC (5 papillary, 6 follicular) for whom withdrawal of thyroid hormone suppression therapy (THST), the standard method to increase serum TSH, was not an option. Indications for rhTSH use in these patients included inability to tolerate withdrawal of thyroid hormones due to very poor physical condition or inability to achieve sufficient serum TSH levels after THST withdrawal. Ten patients had undergone thyroidectomy, and most (9 of 11) had received prior ablative RIT after THST withdrawal. Baseline thyroglobulin levels ranged from 25 to nearly 30,000 ng/mL, reflecting the heterogeneity of the patient population. In 7 cases (5 patients), posttherapy thyroglobulin levels assessed at a mean of 4.3 months (range, 2-10 months) after 131I therapy were decreased by at least 30% compared to pretherapy levels. In follow-up visits, an additional 3 patients showed marked clinical improvement or decreased or stabilized tumor burden in whole body scans compared to pretherapy scans. Three patients died of progressive disease within 2 months of therapy before follow-up assessments occurred. No adverse events were reported among the 8 surviving patients. The results suggest that rhTSH offers a promising alternative to THST withdrawal to allow ablative RIT after effective TSH stimulation in patients with advanced recurrent DTC who would not otherwise be able to receive this treatment. This therapeutic indication extends the clinical potential of this new agent, already demonstrated to be effective for use with 131I for diagnostic purposes.

Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, Cooper DS, Graham KE, Braverman LE, Skarulis MC, Davies TF, DeGroot LJ, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Becker DV, Maxon HR, Cavalieri RR, Spencer CA, McEllin K, Weintraub BD, Ridgway EC. · Division of Endocrinology, University of Colorado Health Sciences Center, Denver 80262, USA. · J Clin Endocrinol Metab. · Pubmed #10566623 links to  free full text

Abstract: Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

Verburg FA, Mäder U, Luster M, Reiners C. · Department of Nuclear Medicine, Würzburg University, Würzburg, Germany. · Eur J Endocrinol. · Pubmed #19158232 No free full text.

Abstract: OBJECTIVE: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) show considerable differences in disease stage at initial presentation. The aim of this study was to investigate whether there are differences in tumour-specific survival if initial staging is accounted for. DESIGN: Retrospective chart review study. PATIENTS: The study sample comprised 875 PTC and 350 FTC patients (856 females, 369 males, mean age 47.8 years) treated in our hospital from 1978 to 2002. All patients received total thyroidectomy with subsequent I-131 ablation except for those patients with an isolated papillary microcarcinoma. METHODS: Kaplan-Meier analyses and Cox-regression analyses were performed to assess the influence of histology on thyroid cancer-specific survival. RESULTS: FTC patients were on average older, more likely to be male, presented with a larger tumour and more frequently had multifocal carcinoma and distant metastases than PTC patients, whereas they presented less frequently with extrathyroidal invasion or lymph node metastases. Twenty-year tumour-specific survival in PTC was 90.6% and in FTC 73.7% (P<0.001). In multivariate analysis the presence of distant metastases (P<0.001), age (P<0.001), tumour size (P=0.001) and the presence of extrathyroidal invasion (P=0.007), but not histology (P=0.26), were independent determinant variables for tumour-specific survival. CONCLUSION: There is no difference in tumour-specific survival between PTC and FTC when accounting for the presence of metastases, age, tumour size and the presence of extrathyroidal invasion.

Freudenberg LS, Jentzen W, Marlowe RJ, Koska WW, Luster M, Bockisch A. · Department of Nuclear Medicine, University of Duisburg/Essen, Essen, Germany. · Exp Clin Endocrinol Diabetes. · Pubmed #18058605 No free full text.

Abstract: AIM: Publications on 124-iodine (124I-)-positron emission tomography/computed tomography (PET/CT) dosimetry contain few if any data on pediatric patients with differentiated thyroid carcinoma (DTC). Aim of our study is to determine safety and informativeness of 124I-PET/CT dosimetry in DTC patients<or=18 yrs old. MATERIAL AND METHODS: We retrospectively analysed the data of 3 years of consecutive procedures (n-5) in children (n-4, 11-15 years). We acquired whole-body 124I-PET emission data 4, 24, 48, 72 and 96 hr, and 124I-PET/CT data 25 hr after oral 124I administration (22-26 MBq). Using these data, we calculated the thyroid remnant or metastatic lesion dose in Gy per GBq of 131-iodine (131I) (RDpA or LDpA, respectively). We measured with a well counter radiation counts of blood samples taken at 2, 4, 24, 48, 72 and 96 hr, and with an uncollimated NaI detector, whole-body clearance at approximately those times. Using these data, we calculated each patient's critical blood activity (CBA), the maximum 131I activity avoiding the putative>2Gy blood dose portending serious myelotoxicity. RESULTS: Besides hypothyroid fatigue, no symptoms were noted. In 4 dosimetry procedures before the first radioiodine therapy, RDpAs were generally high (median 288 Gy/GBq, range 59-648 Gy/GBq). LDpAs (4 lymph node metastases) were much lower (median 6.5 Gy/GBq, range 1-9 Gy/GBq). CBAs were high (median 26 GBq, range 19-42, n=5). Disease management was modified or disease extent clarified in 2/4 patients. CONCLUSIONS: A standard adult 124I-PET/CT dosimetry protocol appears to be safe and informative in pediatric DTC patients.

Dietlein M, Dressler J, Eschner W, Grünwald F, Lassmann M, Leisner B, Luster M, Moser E, Reiners C, Schicha H, Schober O, Anonymous00268, Anonymous00269. · Kliniken und Polikliniken für Nuklearmedizin der Universität zu Köln, 50924 Köln. · Nuklearmedizin. · Pubmed #17938757 No free full text.

Abstract: The procedure guideline for radioiodine therapy (RIT) of differentiated thyroid cancer (version 3) is the counterpart to the procedure guideline for (131)I whole-body scintigraphy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Recommendation for ablative (131)I therapy is given for all differentiated thyroid carcinoma (DTC) >1 cm. Regarding DTC < or =1 cm (131)I ablation may be helpful in an individual constellation. Preparation for (131)I ablation requires low iodine diet for two weeks and TSH-stimulation by withdrawal of thyroid hormone medication or by use of recombinant human TSH (rhTSH). The advantages of rhTSH (no symptoms of hypothyroidism, lower blood activity) and the advantages of endogenous TSH-stimulation (necessary for (131)I-therapy in patients with metastases, higher sensitivity of (131)I whole-body scan) are discussed. In most centers standard activities are used for (131)I ablation. If pretherapeutic dosimetry is planned, the diagnostic administration of (131)I should not exceed 1-10 MBq, alternative tracers are (123)I or (124)I. The recommendations for contraception and family planning are harmonized with the recommendation of ATA and ETA. Regarding the best possible protection of salivary glands the evidence is insufficient to recommend a specific setting. To minimize the risk of dental caries due to xerostomia patients should use preventive strategies for dental hygiene.

Dietlein M, Dressler J, Eschner W, Grünwald F, Lassmann M, Leisner B, Luster M, Reiners C, Schicha H, Schober O, Anonymous00266, Anonymous00267. · Kliniken und Polikliniken für Nuklearmedizin der Universität zu Köln, 50924 Köln. · Nuklearmedizin. · Pubmed #17938756 No free full text.

Abstract: Version 3 of the procedure guideline for (131)I whole-body scintigraphy (WBS) is the counterpart to the procedure guideline for radioiodine therapy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. (131)I WBS 3-6 months after (131)I ablation remains a standard procedure in an endemic area for thyroid nodules and the high frequency of subtotal surgical procedures. Follow-up without (131)I WBS is only justified if the following preconditions are fulfilled: low-risk group pT1-2, pN0 M0 with histopathologically confirmed pN0, (131)I uptake <2%, (131)I WBS during ablation without any suspicious lesion, stimulated thyroglobulin (Tg)-level 3-6 months after ablation <2 ng/mL, and absence of anti-thyroglobulin-antibodies with normal recovery-testing. If patients from the low-risk group show normal (131)I WBS 3-6 months after ablation and stimulated Tg is of <2 ng/mL, there will be no need for additional routine (131)I WBS. If patients from the high-risk group show normal (131)I WBS and stimulated Tg-level of <2 ng/mL 3-6 months after ablation, the follow-up care should include repeated stimulated Tg-measurements. If the Tg-level remains below 2 ng/mL, an additional (131)I WBS will be not necessary. The recommended intervals for stimulated Tg-testing are adapted to the prior intervals for (131)I WBS-testing in the high-risk group. Increased anti-thyroglobulin-antibodies or incomplete recovery-testing make an individual strategy of follow-up care necessary, which include (131)I WBS.

Mernagh P, Campbell S, Dietlein M, Luster M, Mazzaferri E, Weston AR. · Health Technology Analysts Pty Ltd, PO Box 133, Balmain, Sydney 2041, Australia. · Eur J Endocrinol. · Pubmed #16914594 links to  free full text

Abstract: OBJECTIVE: This investigation evaluated the cost-effectiveness of radioiodine remnant ablation following preparation with recombinant human TSH (rhTSH), compared with the standard preparation, whereby patients are rendered hypothyroid. DESIGN: The economic evaluation relates to patients with well differentiated thyroid cancer who have undergone thyroidectomy, but have no metastases. The evaluation takes a societal perspective, considering costs and benefits to all parties. The benefits were expressed in units of quality-adjusted life years (QALY), so differences in life expectancy were captured with consideration of quality of life. METHODS: A lifetime Markov model with Monte Carlo simulation of 100,000 patients was used to assess cost per QALY gained. The clinical inputs were sourced from a multi-centre, randomised controlled trial comparing remnant ablation success after rhTSH-preparation with hypothyroid preparation. The model applied German unit costs, however, the structure is generalisable to other jurisdictions. The additional cost of rhTSH procurement and administration is considered relative to the clinical benefits and cost offsets. These included avoidance of hypothyroidism, increased work productivity, earlier discharge from radioprotection and a theoretical reduction in the risk of secondary malignancy. The latter two benefits relate to faster radioiodine clearance after rhTSH preparation. RESULTS: The additional benefits of rhTSH (0.0495 QALY) are obtained with an incremental societal cost of 47 euro, equating to an incremental cost per QALYof 958 euro. Sensitivity analyses had only a modest impact upon cost-effectiveness, with all one-way sensitivity results remaining under 15,000 euro/QALY. CONCLUSIONS: The use of rhTSH prior to radioiodine ablation represents good value-for-money with the benefits to patient and society obtained at modest net cost.

Hänscheid H, Lassmann M, Luster M, Thomas SR, Pacini F, Ceccarelli C, Ladenson PW, Wahl RL, Schlumberger M, Ricard M, Driedger A, Kloos RT, Sherman SI, Haugen BR, Carriere V, Corone C, Reiners C. · Klinik und Poliklinik für Nuklearmedizin, Universität Würzburg, D-97080 Würzburg, Germany. · J Nucl Med. · Pubmed #16595499 links to  free full text

Abstract: Technical aspects and results of the dosimetric assessments of postoperative radioiodine ablation in the framework of an international, prospective, controlled, randomized, comparative study of the effectiveness of ablation therapy with 3.7 GBq (131)I in differentiated thyroid cancer after stimulation with recombinant human TSH (rhTSH) or by thyroid hormone withdrawal (THW) are presented. METHODS: Sixty-three patients were randomized after thyroidectomy to either the THW or the rhTSH group. Scintigraphic neck images were acquired starting 48 h after radioiodine administration to assess biokinetics in the thyroid remnant. The activity in blood samples was quantified and data from whole-body probe measurements and scintigraphic whole-body scans were combined to deduce retention curves in blood and whole body, respectively. The absorbed dose to the blood was calculated using a modified approach based on the formalism of the MIRD Committee of the Society of Nuclear Medicine. RESULTS: The effective half-time in the remnant thyroid tissue was significantly longer after rhTSH than THW (67.6 +/- 48.8 vs. 48.0 +/- 52.6 h, respectively; P = 0.01), whereas the observed differences of the mean 48-h (131)I uptakes (0.5% +/- 0.7% vs. 0.9% +/- 1.0% after THW; P = 0.1) and residence times (0.9 +/- 1.3 vs. 1.4 +/- 1.5 h after THW; P = 0.1) between the rhTSH and THW groups were not statistically significant. The specific absorbed dose to the blood was significantly (P <0.0001) lower after administration of rhTSH (mean, 0.109 +/- 0.028 mGy/MBq; maximum, 0.18 mGy/MBq) than after THW (mean, 0.167 +/- 0.061 mGy/MBq; maximum, 0.35 mGy/MBq), indicating that higher activities of radioiodine might be safely administered after exogenous stimulation with rhTSH. CONCLUSION: Indication of an influence of the residence time of radioiodine in the blood on the fractional uptake into thyroid remnant was found. A novel regimen is proposed in which therapeutic activities to be administered are determined from the individual specific blood dose.

Pacini F, Ladenson PW, Schlumberger M, Driedger A, Luster M, Kloos RT, Sherman S, Haugen B, Corone C, Molinaro E, Elisei R, Ceccarelli C, Pinchera A, Wahl RL, Leboulleux S, Ricard M, Yoo J, Busaidy NL, Delpassand E, Hanscheid H, Felbinger R, Lassmann M, Reiners C. · Section of Endocrinology, Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. · J Clin Endocrinol Metab. · Pubmed #16384850 links to  free full text

Abstract: CONTEXT: After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue. This procedure has been performed with the patient in the hypothyroid state to promote endogenous TSH stimulation and is often associated with hypothyroid symptoms and impaired quality of life. OBJECTIVE AND INTERVENTION: This international, randomized, controlled, multicenter trial aimed to compare the efficacy and safety of recombinant human TSH (rhTSH) to prepare euthyroid patients on L-thyroxine therapy (euthyroid group) to ablate remnant thyroid tissue with 3.7 GBq (100 mCi) 131I, compared with that with conventional remnant ablation performed in the hypothyroid state (hypothyroid group). Quality of life was determined at the time of randomization and ablation. After the administration of the 131-I dose, the rate of radiation clearance from blood, thyroid remnant, and whole body was measured. RESULTS: The predefined primary criterion for successful ablation was "no visible uptake in the thyroid bed, or if visible, fractional uptake less than 0.1%" on neck scans performed 8 months after therapy and was satisfied in 100% of patients in both groups. A secondary criterion for ablation, an rhTSH-stimulated serum thyroglobulin concentration less than 2 ng/ml, was fulfilled by 23 of 24 (96%) euthyroid patients and 18 of 21 (86%) hypothyroid patients (P = 0.2341). Quality of life was well preserved in the euthyroid group, compared with the hypothyroid group, as demonstrated by their lower pretreatment scores on the Billewicz scale for hypothyroid signs and symptoms, 27 +/- 7 vs. 18 +/- 4 (P < 0.0001) and their significantly higher Short Form-36 Health Assessment Scale scores in five of eight categories. Euthyroid patients had a statistically significant one third lower radiation dose to the blood, compared with patients in the hypothyroid group. CONCLUSIONS: This study demonstrates comparable remnant ablation rates in patients prepared for 131I remnant ablation with 3.7 GBq by either administering rhTSH or withholding thyroid hormone. rhTSH-prepared patients maintained a higher quality of life and received less radiation exposure to the blood.

Luster M, Felbinger R, Dietlein M, Reiners C. · Department of Nuclear Medicine, University of Würzburg, Germany. · Thyroid. · Pubmed #16279848 No free full text.

Abstract: The study objective was to elucidate clinical, quality-of-life, and pharmacoeconomic effects of hypothyroidism secondary to thyroid hormone withdrawal (withdrawal) in athyroid patients with differentiated thyroid cancer (DTC). We also intended to compare societal costs of withdrawal and recombinant human thyroid-stimulating hormone administration (rhTSH) in this population. We mailed a 13-item pilot survey to patients with DTC who had undergone withdrawal before diagnostic whole-body scan (dxWBS). Using survey results and actual and estimated cost data, we retrospectively constructed a societal cost model comparing withdrawal versus rhTSH and performed a sensitivity analysis by increasing the conservatism of 8 assumptions about withdrawal costs. One hundred thirty (55%) of 236 patients answered the questionnaire. Among respondents, 92% had symptomatic and 85% multisymptomatic hypothyroidism. Almost half sought medical attention for hypothyroid complaints. Approximately one third drove motor vehicles while hypothyroid. Median absence from salaried work was 11 days per withdrawal. In the pharmacoeconomic model, societal costs per dxWBS were approximately 326 euro (25%) greater for withdrawal than for rhTSH. In the sensitivity analysis, societal costs of rhTSH exceeded those of withdrawal by approximately 307 euro (30%). In conclusion, hypothyroidism secondary to withdrawal causes important morbidity, safety risks, and productivity impairment. rhTSH avoids these drawbacks at roughly equivalent societal cost to that of withdrawal.

Lassmann M, Luster M, Hänscheid H, Reiners C. · No affiliation provided · J Nucl Med. · Pubmed #15872368 links to  free full text

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