Search

The purpose of the present guidelines on the (131)I therapy of benign thyroid disorders formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians on how to treat benign thyroid conditions employing optimal (131)I activities. The recommendations were formulated based on recent literature and expert opinion regarding rationale, indications and contraindications for the use of (131)I procedures, as well as the adequate (131)I activities in different thyroid disorders, and the administration and patient preparation techniques to be used. Recommendations are also provided on history and examinations before (131)I therapy, patient counselling and precautions associated with (131)I therapy. Furthermore, potential side effects and alternative treatment modalities are reviewed. Special attention is paid to these aspects in the treatment of children undergoing this procedure.

Introduction: In delusional infestation (DI), as with other non-schizophrenic psychotic disorders, little is known about the neural basis and the mechanisms of antipsychotic treatment. We aimed at investigating the brain circuitry involved in DI and the role of postsynaptic D2 receptors in mediating the effects of antipsychotics by means of multimodal neuroimaging., Methods: In Case 1, a patient with DI (initially drug-induced), cerebral glucose metabolism and dopaminergic neurotransmission were studied in the untreated state (FDG-PET, FDOPA-PET, 123I-FP-CIT-SPECT, and IBZM-SPECT) and after effective aripiprazole treatment (FDG-PET and IBZM-SPECT), with negative drug screenings at both imaging sessions. In Case 2 (DI secondary to mild vascular encephalopathy) cerebral perfusion and gray matter volume changes were investigated in the untreated state and compared to N=8 [corrected] age-matched healthy controls (MRI-based CASL and VBM)., Results: In Case 1, before treatment, glucose metabolism was left-dominant in the thalamus and the putamen. Pre- and postsynaptic dopaminergic neurotransmissions were altered in the striatum, again mainly the left putamen. Full remission to aripiprazole was associated with 63 to 78% striatal D2 receptor occupancy and glucose metabolism changes in the bilateral thalamus. In Case 2, significant perfusion and GMV changes were observed in the bilateral putamen, frontal and parietal somatosensory cortices as compared to controls. Symptoms partially remitted to ziprasidone therapy., Discussion/conclusion: Six imaging techniques were first used to study the neural basis of DI and mechanisms of antipsychotic therapy. The study provides first low-level evidence in vivo evidence of fronto-striato-thalamo-parietal network to mediate core symptoms of DI, i.e. a priori brain regions involved in judgment (frontal cortex), sensory gating (thalamus) and body perception (dorsal striatum, thalamus and somatic cortices). This is also the first report of effective treatment with aripiprazole in drug-induced DI and with ziprasidone in organic DI, adding to existing limited evidence that SGAs are helpful in various forms of DI. Effective antipsychotic treatment seems to depend on blocking striatal D2 receptors with similar occupancy rates as in schizophrenia. Larger samples are needed to confirm our preliminary findings and further evaluate their relevance for the different forms of DI., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Ultrasound, scintigraphy and sonographically guided fine-needle biopsy are the cornerstones in the diagnostic work-up multinodular goitre. Subsequent decisions for adequate treatments should be based on accurate tests to avoid unnecessary intervention. Especially in areas with endemic goitre a preselection of patients for the most effective procedure e.g. surgical or medical treatment is mandatory. Autoimmune hyperthyroidism (Graves' disease), solitary hyperfunctioning thyroid nodules and toxic multinodular goitre (Plummer's disease) constitute a clear indication for radioiodine treatment in many cases. Recently, there is an emerging role for I-131 in the treatment for so called subclinical hyperthyroidism caused by either of three first entities and for patients with non-toxic goitre, in whom surgery is not an option. These patients with large non toxic goitre encompass a group of patients who are euthyroid but may benefit from diminishment of thyroid volume. We review the spectrum of diagnostic tests and provide some recommendations regarding (nuclear medicine) therapy.

Purpose: Approximately 5% of differentiated thyroid carcinomas are of familial origin. These familial nonmedullary thyroid carcinomas (FNMTC) have an increased risk of multifocal disease and lymph node involvement. Consequently, higher recurrence rates and decreased disease-specific survival rates are described. The best surgical approach is discussed controversially., Patients and Methods: A survey among the international members of the German Society of Endocrine Surgeons revealed 20 families with two or more first-degree relatives with FNMTC. The mean age of the 41 patients (30 female, 11 male) with FNMTC was 40.6 years (18-73 years)., Results: Total thyroidectomy was performed in 31 of 41 patients (76%). Ninety-five percent of the tumors were papillary carcinomas. Two of 41 patients had follicular carcinomas. Ten patients (24%) with papillary carcinomas were diagnosed with Hashimoto's thyroiditis. The mean tumor size was 1.45 cm. FNMTC was multifocal in 12 patients (29%). A systematic lymph node dissection was performed in 21 of 41 patients (51%). Lymph nodes metastases were found in seven of these 21 patients. Twenty-eight of the patients (68%) underwent postoperative radioiodine ablation. After a mean follow-up of 7.2 years, 39 patients (95%) were disease free. One patient developed local recurrence and lung metastases, 10 and 25 years, respectively, after initial diagnosis. Another patient died 2 years postoperatively from advanced metastatic disease., Conclusions: FNMTC is associated with an early onset of small, mostly papillary thyroid carcinomas and an increased risk of multifocality and lymph node involvement. Total thyroidectomy and systematic neck dissection are recommended together with radioiodine ablation. Screening for first-degree relatives should start at age 18 years.

Aim: Withdrawal of levothyroxine with resultant hypothyroidism is still used in preparation for I-131 diagnostic whole-body scan (DWBS) and thyroglobulin (TG)-measurement in patients afflicted with differentiated thyroid cancer (DTC). Recombinant human thyroid-stimulating hormone (rhTSH) enhances TSH stimulation obviating the clinical and economical consequences of hypothyroidism. Primary aim of this study was an intraindividual comparison of diagnostic follow-up measurements under these two sets of conditions by taking clinical and socio-economic parameters into account. Second aim was to determine a clear patient preference for the one method or the other., Methods: This non-interventional observational study included patients (n=192 signed informed consent, n=128 protocol compliant patients without need for therapeutic intervention) with DTC first treated by thyroidectomy and radioiodine ablation. Control visits including I-131 DWBS were planned at 3-6 months post-thyroidectomy after a phase (KU 1) of thyroid hormone withdrawal (THW) and again after 6-12 months later in a euthyroid state under exogenous stimulation with rhTSH (KU 2). Study design was open, prospective and multicentric. Data collected consisted of patient information (SF-12 (®) Health Survey), thyroid-specific results of clinical examinations and several aspects of daily life, e. g., employment, days of absence from work and other economic aspects., Results: In contrast to KU 1, in KU 2 there is a highly significant improvement (p<0.0001) in all studied clinical symptoms and aspects of managing daily life. A significant increase of the SF-12 (®) health survey score could also be identified. Mental score showed a higher increase than physical score. Included patients were less absent from work before KU 2, (absent 4.5%, median 4 days in euthyroid state [range 2-5 d]), vs. before KU 1 (absent 47.8%, median 10 days in hypothyroid state [range 1-30 d]). After KU 2 7.7% of the euthyroid patients was absent from work (median 5 days) while 37.5% was after KU 1 (median 6 days)., Conclusion: Included patients benefited subjectively and objectively from the use of rhTSH for diagnostic procedures in the treatment of DTC. A clear preference (127 of 128) of analyzed patients could be identified for exogenous stimulation with rhTSH., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Adjuvant therapy of differentiated thyroid cancer with radioactive iodine ((131)I) is a standard procedure for the ablation of remnant thyroid tissue following surgery and for the treatment of iodine-avid metastases. Presently, there are two dosimetric concepts for the treatment of thyroid cancer using radioiodine: a) the bone marrow dose limited approach and b) lesion-based dosimetry. Both concepts and their clinical applications are described. In addition, the use of (124)I as a diagnostic and dosimetric agent is discussed. Treatment of children and adolescents with radioiodine requires special precautions; individualized approaches in this setting are reviewed. The limitations of treatments aiming at high absorbed doses are addressed as well as the doses to normal organs. Finally, new concepts for further elaborating the potential of thyroid cancer treatment using (131)I are introduced.

Objective: To identify and compare prognostic classification systems based on basic tumour characteristics that were developed and/or validated for differentiated thyroid carcinoma (DTC)., Design: Retrospective chart study., Methods: Literature was studied using PubMed. Fifteen different prognostic classification systems were identified, of which seven were developed or validated for DTC patients and were based on basic tumour characteristics. These systems were applied to 1225 DTC patients who were treated in our hospital between 1978 and 2002., Results: Log-rank analysis of Kaplan-Meier cancer-specific survival curves showed that the curve of the Tumor, Lymph-Node, Metastasis (TNM) system had the greatest discriminatory power (log-rank test, log P = -84.9). Cox-regression analysis showed that the TNM system was the most powerful determinant of cancer-specific survival curves. Proportion of variance explained (PVE) analysis showed that the TNM system had the highest PVE., Conclusion: Of the prognostic classification systems analysed in this study, the TNM system performs best in all the three analyses, and is therefore the most suitable for predicting outcome in DTC-patients.

Purpose: In patients with advanced differentiated thyroid carcinoma (DTC), therapy with the highest safe (131)I activity is desirable to maximize the tumour radiation dose yet avoid severe myelotoxicity. Recently, the European Association of Nuclear Medicine (EANM) published a standard operational procedure (SOP) for pre-therapeutic dosimetry in DTC patients incorporating a safety threshold of a 2 Gy absorbed dose to the blood as a surrogate for the red marrow. We sought to evaluate the safety and effectiveness in everyday tertiary referral centre practice of treating advanced DTC with high (131)I activities chosen primarily based on the results of dosimetry following this SOP., Methods: We retrospectively assessed toxicity as well as biochemical and scintigraphic response in our first ten patients receiving such therapy for advanced DTC., Results: The 10 patients received a total of 13 dosimetrically guided treatments with a median administered activity of 14.0 GBq (range: 7.0-21.4 GBq) (131)I. After 6 of 13 treatments in 6 of 10 patients, short-term side effects of (131)I therapy, namely nausea, vomiting or sialadenitis, were observed. Leukocyte and platelet counts dropped significantly in the weeks after (131)I treatment, but returned to pre-treatment levels by 3 months post-therapy. Serum thyroglobulin levels decreased after 12 of 13 treatments (median reduction: 58%) in 9 of 10 patients., Conclusion: In our initial patient cohort, high-activity (131)I therapy for advanced DTC based on pre-therapeutic blood dosimetry following the EANM SOP was safe and well tolerated. Such treatment almost always produced a partial biochemical tumour response.

Background: 18-Fluorine-fluorodihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET) is a sensitive method for detecting medullary thyroid carcinoma (MTC). The advent of PET/computed tomography (CT) has enabled more sensitive and specific lesion identification using various tracers in many other tumors. The aim of this study was therefore to test the hypothesis that combined (18)F-DOPA PET/CT more accurately detects MTC lesions than each modality does alone., Methods: Twenty-eight consecutive (18)F-DOPA PET, CT, and (18)F-DOPA PET/CT scans of patients followed up for sporadic MTC or multiple endocrine neoplasia 2 syndrome-associated MTC were reviewed retrospectively in randomized sequence by two blinded readers, one a nuclear medicine physician and the other a radiologist, with extensive experience interpreting such images., Results: Of 18 lesions detected concurrently by the three modalities, PET identified all as positive for MTC, but was unable to definitively localize 4 (22%) lesions. CT could definitively localize all 18 lesions, but could not definitively diagnose or exclude MTC in 6 (33%) lesions. Further, CT falsely identified as MTC-negative one lesion that was judged to be MTC-positive by both PET and PET/CT. Only PET/CT scans accurately characterized and localized all 18 lesions. On a per patient basis, the sensitivity of (18)F-DOPA PET/CT for MTC was 74% and the specificity, 100%. In the present series, no truly MTC-positive (18)F-DOPA PET/CT case was found in patients with basal human calcitonin (hCt) levels under 60 pg/mL, and conversely, no truly MTC-negative PET/CT case was found in patients with basal hCt over 120 pg/mL. Between hCt concentrations of 60 and 150 pg/mL true-negative, false-negative, and true-positive scans all were obtained. (18)F-DOPA PET/CT had 100% sensitivity and specificity when hCt at the time of scanning was over 150 pg/mL, the threshold at which the 2009 American Thyroid Association guidelines recommend performing additional imaging including (18)F-DOPA PET/CT., Conclusions: (18)F-DOPA PET/CT allows for a more accurate diagnosis and localization of MTC lesions than do (18)F-DOPA PET or CT alone. Supporting the recent American Thyroid Association recommendations on additional imaging in MTC, (18)F-DOPA PET/CT appears to have 100% sensitivity in patients with hCt over 150 pg/mL.

Purpose: In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor (18)F-fluorodihydroxyphenylalanine ((18)F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined (18)F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone., Methods: (18)F-DOPA PET, CT and (18)F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology., Results: Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of (18)F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value., Conclusion: (18)F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do (18)F-DOPA PET or CT alone.

In patients with primary hyperparathyroidism (pHPT), positive preoperative localization studies enable to perform a minimally invasive approach for parathyroid surgery. However, current imaging techniques are not always successful. We therefore conducted a study to determine the sensitivity of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT) in localizing parathyroid adenomas in pHPT. Met-PET/CT scans of the neck and mediastinum of 33 patients undergoing parathyroidectomy for primary HPT were compared with intraoperative and histological findings. Primary HPT was caused by a single gland adenoma in 30 patients, while another 3 patients had multiglandular disease. Met-PET/CT scan correctly located a single gland adenoma in 25 out of 30 (83%) patients with pHPT, among them 2 patients with persistent disease, 7 patients with prior neck surgery, and 8 patients with concomitant thyroid nodules. In 3 patients with multiglandular disease, Met-PET/CT showed only one enlarged parathyroid gland in two individuals and was negative in the third patient. Statistical analysis found a significant correlation between true-positive results and the weight (2.42+/-4.05 g) and diameter (2.0+/-1.18 cm) of parathyroid adenomas while the subgroup with false negative findings had significantly smaller (0.98+/-0.54 cm) and lighter (0.5+/-0.38 g) glands. Sensitivity was 83% for single gland adenomas and 67% for multiglandular disease. Met-PET/CT correctly localized 83% of single gland parathyroid adenomas in patients with pHPT. However, preoperative localization of multiglandular disease due to double adenomas or parathyroid hyperplasia remained difficult.

Unlabelled: To improve radioimmunotherapy with anti-CD66 antibody, a physiologically based pharmacokinetic (PBPK) model was developed that was capable of describing the biodistribution and extrapolating between different doses of anti-CD66 antibody., Methods: The biodistribution of the (111)In-labeled anti-CD66 antibody of 8 patients with acute leukemia was measured. The data were fitted to 2 PBPK models. Model A incorporated effective values for antibody binding, and model B explicitly described mono- and bivalent binding. The best model was selected using the corrected Akaike information criterion. The predictive power of the model was validated comparing simulations and (90)Y-anti-CD66 serum measurements. The amount of antibody (range, 0.1-4 mg) leading to the most favorable therapeutic distribution was determined using simulations., Results: Model B was better supported by the data. The fits of the selected model were good (adjusted R(2) > 0.91), and the estimated parameters were in a physiologically reasonable range. The median deviation of the predicted and measured (90)Y-anti-CD66 serum concentration values and the residence times were 24% (range, 17%-31%) and 9% (range, 1%-64%), respectively. The validated model predicted considerably different biodistributions for dosimetry and therapeutic settings. The smallest (0.1 mg) simulated amount of antibody resulted in the most favorable therapeutic biodistribution., Conclusion: The developed model is capable of adequately describing the anti-CD66 antibody biodistribution and accurately predicting the time-activity serum curve of (90)Y-anti-CD66 antibody and the therapeutic serum residence time. Simulations indicate that an improvement of radioimmunotherapy with anti-CD66 antibody is achievable by reducing the amount of administered antibody; for example, the residence time of the red marrow could be increased by a factor of 1.9 +/- 0.3 using 0.27 mg of anti-CD66 antibody.

The purpose of this study was to investigate whether the expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ toxicity induced by chemicals in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or a neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities. Similarly, administration of methyl parathion (MP) resulted in neurotoxicity in the rats as evidenced from the inhibition of acetyl cholinesterase activity in their blood. Administration of either chemical also resulted in mild hematotoxicity in the rats. Microarray analysis of the global gene expression profile of rat blood identified distinct gene expression markers capable of detecting and distinguishing hepatotoxicity and neurotoxicity induced by AP and MP, respectively. Differential expressions of the marker genes for hepatotoxicity and neurotoxicity were detectable in the blood earlier than the appearance of the commonly used clinical markers (serum transaminases and acetyl cholinesterase). The ability of the marker genes to detect hepatotoxicity and neurotoxicity was further confirmed using the blood samples of rats administered additional hepatotoxic (thioacetamide, dimethylnitrobenzene, and carbon tetrachloride) or neurotoxic (ethyl parathion and malathion) chemicals. In summary, our results demonstrated that blood gene expression markers can detect and distinguish target organ toxicity non-invasively.

Purpose: To compare disease-specific survival and recurrence-free survival (RFS) after successful (131)I ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as high-risk according to the European Thyroid Association 2006 consensus statement., Methods: Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.1+/-4.6 months after ablation. Of these 509 patients, 169 were defined as high-risk., Results: After a mean follow-up of 81+/-64 months (range 4-306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 12-59 months) after ablation. RFS for the duration of follow-up was 96.6% according to the Kaplan-Meier method. RFS did not differ between high-risk and low-risk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged 45 years at diagnosis (p=0.018)., Conclusion: After (near) total thyroidectomy and successful (131)I ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification.

After total thyroidectomy for differentiated thyroid carcinoma (DTC), I-131 ablation is usually recommended in all patients but those classified as "very low risk", and mandatory for all patients classified as "high risk". For those classified as "low risk" there is some discussion as to whether I-131 ablation should still be performed. In this review various staging systems for classifying patients as "very low risk" "low risk" or "high risk" are discussed, followed by an overview of why I-131 ablation remains an eminently sensible idea in "low risk" patients.

A simple method is presented to estimate the radiation-absorbed dose to the blood after radioiodine administration from a single external measurement of the whole-body retention in patients suffering from differentiated thyroid cancer. The blood dose is calculated applying the formalism of the Medical International Radiation Dose Committee under the assumptions that whole-body activity decays exponentially and that 14% of the whole-body residence time can be attributed to the blood. Accuracy and applicability of the method were tested based on data from 29 assessments, 18 pre-therapeutic tracer studies, and 11 ablation therapies, with whole-body and blood-retention measurements over at least 4 days. The mean of the absolute deviations between estimates and actual blood doses was found to be 14%, if external whole-body counting was performed on day 1 or 2 after radioiodine administration. This simple formalism is: 1) applicable to pre-therapeutic dosimetry for remnant ablation or treatment of metastases in a blood dose-based treatment concept and 2) applicable to blood-dose estimates after radioiodine therapy to determine radiation exposure. When combined with a measurement of the whole body retention 1 or 2 days after radioiodine administration this single time-point method closely approximates the classic, yet much more labor intensive multi-day dosimetry that measures both blood and whole-body activities.

Background: We previously demonstrated comparable thyroid remnant ablation rates in postoperative low-risk thyroid cancer patients prepared for administration of 3.7GBq (131)I (100 mCi) after recombinant human (rh) TSH during T(4) (L-T4) therapy vs. withholding L-T4 (euthyroid vs. hypothyroid groups). We now compared the outcomes of these patients 3.7 yr later., Patients and Methods: Fifty-one of the 63 original patients (28 euthyroid, 23 hypothyroid) participated. Forty-eight received rhTSH and serum thyroglobulin (Tg) sampling. A (131)I whole-body scan was performed in 43 patients, and successful ablation was defined by criteria from the previous study. Based on the criterion of uptake less than 0.1% in thyroid bed, 100% (43 of 43) remained ablated. When no visible uptake instead was used, five patients (four euthyroid, one hypothyroid) had minimal visible activity. When the TSH-stimulated Tg criterion was used, only two of 45 (one euthyroid, one hypothyroid) had a stimulated Tg level greater than 2 ng/ml., Results: No patient in either group died, and no patient declared disease free had sustained tumor recurrence. Nine (four euthyroid, five hypothyroid) had received additional (131)I between the original and current studies due to detectable Tg or imaging evidence of disease; with follow-up, all now had a negative rhTSH-stimulated whole-body scan and seven (three euthyroid, four hypothyroid) had a stimulated serum Tg less than 2 ng/ml., Conclusions: In conclusion, after a median 3.7 yr, low-risk thyroid cancer patients prepared for postoperative remnant ablation either with rhTSH or after L-T4 withdrawal were confirmed to have had their thyroid remnants ablated and to have comparable rates of tumor recurrence and persistence.

Context: Although recombinant human TSH (rhTSH) is widely used in differentiated thyroid cancer (DTC) to aid diagnostic follow-up procedures and radioiodine thyroid remnant ablation, almost all clinical investigation was in adults., Objective: The aim of this study was to characterize rhTSH clinical safety and peak TSH response in DTC patients 18 yr old or younger., Design and Setting: We conducted a retrospective study involving 23 tertiary referral centers in 12 European, Asian, and Oceanian countries., Patients: One hundred DTC patients (69% female, 31% male, 84% papillary, 61% N1, 18% M1) ages 4.9-18 yr at first rhTSH administration were studied., Interventions: A total of 181 rhTSH courses were administered (range, one to eight per patient; 42% of patients received two or more courses), 92% using the approved adult regimen (one 0.9 mg im injection daily on two consecutive days), 34% including thyroid hormone withdrawal for less than 7 d ("mini-THW")., Main Outcome Measures: Clinical adverse event (AE) incidence, type, and severity, and peak post-rhTSH serum TSH concentrations were assessed., Results: No clinical AEs occurred in 88% of rhTSH courses. Most common clinical AEs were nausea (5% of courses) and vomiting (3%). Multiple or severe AEs were rare (0.6% and 2.8% of courses, respectively); serious AEs were absent. Peak TSH concentration post-rhTSH exceeded 25 mU/liter in approximately 98% of courses. In logistic regression analyses, the rhTSH regimen, "mini-THW," peak TSH concentration, body mass index (BMI), or peak TSH concentration/unit of BMI were not associated with clinical AE occurrence. In analyses of covariance, higher BMI was associated with lower peak TSH concentrations., Conclusions: rhTSH was clinically well tolerated in pediatric DTC patients although courses preponderantly comprised the adult regimen, and repeated courses were frequent. Both the adult and reduced-dose regimens almost always sufficiently elevate TSH in children and adolescents.

Background: Intratracheal goiter manifestations caused by ectopic thyroid tissue have occasionally been reported. We report a 42-year-old female who had undergone thyroid surgery twice, which had caused unilateral recurrent laryngeal nerve palsy., Summary: The patient presented with progressive dyspnea. Magnetic resonance imaging showed a recurrent goiter growing through the tracheal wall. She was treated in a multidisciplinary approach; at first she underwent transtracheal laser surgical removal of the intratracheal mass followed by conventional completion thyroidectomy and radioiodine remnant ablation. Thorough histological analysis did not find any signs of malignancy. Currently the patient is disease- and complaint free. As far as we could ascertain, no patient with a recurrent benign goiter growing through the tracheal wall has been reported before., Conclusion: Recurrent benign goiter with intratracheal growth is extremely rare and requires a multidisciplinary approach.

Objective: The objectives of the study was to compare pentagastrin- and calcium-stimulated serum human calcitonin (hCT) levels for nonsmoking healthy adults without evidence of thyroid disorders and determine reference ranges of basal and pentagastrin- and calcium-stimulated serum hCT levels., Design: This was a healthy volunteer study including within-group and intergroup comparisons., Setting: The study was conducted at a tertiary referral center., Subjects: Subjects included 50 healthy, nonsmoking volunteers (25 female; aged 22-57 yr) without evidence of thyroid abnormality., Interventions: hCT was measured using a calcitonin two-site automated chemiluminescent immunometric assay (the most common hCT assay in clinical practice) in serum samples obtained before and 2, 5, and 15 min after iv stimulation using pentagastrin, 0.5 microg/kg body weight, or calcium gluconate, 2.5 mg/kg., Main Outcome Measures: Reference ranges for basal, unstimulated, and pentagastrin- or calcium-stimulated hCT and pentagastrin and calcium tolerability in healthy adults were measured., Results: The 95th percentile basal hCT values did not differ between males and females (5.0 vs. 5.7 pg/ml). The 95th percentile maximal stimulated hCT values rose distinctly after pentagastrin (peak men, 37.8 pg/ml; women, 26.2 pg/ml) and even more so after calcium (peak men, 131.1 pg/ml, women, 90.2 pg/ml). No hCT increase was detected in four of 25 men and 12 of 25 women after pentagastrin vs. none of 24 men and two of 18 women after calcium. Calcium was associated with fewer and less intense adverse effects than was pentagastrin., Conclusion: High-dose calcium is a more potent and better-tolerated hCT stimulator than is pentagastrin. The reference ranges for basal and stimulated hCT established via automated chemiluminescent assay were lower than those reported for other assays.

Objective: To study the relationship between primary tumour size and the risk of advanced disease features (multifocal or locally invasive disease, lymph-node or distant metastases) in differentiated thyroid carcinoma (DTC)., Design: A retrospective chart review study., Patients: The study sample comprised 935 papillary (PTC) and 291 follicular thyroid carcinoma (FTC) patients treated in our hospital from 1978 to 2007., Measurements: Kaplan-Meier analyses and log-rank tests were performed to calculate tumour size-adjusted cumulative risk of advanced disease features., Results: Accounting for primary tumour diameter, there were no significant differences in cumulative risks of multifocal carcinoma (P = 0.12) or distant metastases (P = 0.49) between PTC and FTC. PTC showed higher cumulative risks of local invasion (P < 0.0001) or lymph-node metastases (P < 0.0001). The cumulative risk of tumour multifocality increased 5%/cm of primary tumour diameter. The cumulative risk of local invasion or lymph-node metastases in PTC and of distant metastases in DTC increased exponentially at a threshold tumour diameter of 10 mm. In FTC, lymph-node metastases are associated almost exclusively with primary tumours showing extrathyroidal growth., Conclusions: Starting with a 1 cm primary tumour diameter, increasing tumour size is associated with an exponentially increasing risk of local invasion or lymph-node or distant metastases of DTC. The current classification of carcinomas < 2 cm as T1 is therefore questionable.

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.

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.

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.

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.

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.

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 patients2Gy 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.

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.

The transforming growth factor-beta1 (TGF-beta1) is involved in post-ischemic neuronal rescue and in beta-amyloid turn-over. We hypothesized that the risk for dementia and related neuropathologies is modified by the TGF-beta1 functional genetic variants. The association of the TGF-beta1+29T-->C polymorphism with dementia was examined in a sample of 261 cases and 491 controls from the Honolulu-Asia Aging Study, including 282 subjects with autopsy data. Dementia was assessed in 1991 and 1994 by a multi-step protocol and standardized diagnostic criteria. The analysis was adjusted for demographic and vascular factors. Compared to the TT genotype, the TC and the CC genotypes were associated with a reduced risk for vascular dementia (OR(TC)=0.28, 95% confidence interval (CI): 0.1-0.9; OR(CC)=0.28, CI: 0.1-0.9), microinfarcts (OR(CC)=0.31, CI: 0.13-0.71) and cerebral amyloid angiopathy (OR(CC)=0.48, CI: 0.2-0.9). The CC genotype was associated with an increase risk of neocortical plaques (OR(CC)=4.34, CI: 1.6-11.8). These preliminary data suggest that the TGF genetic variability may be important in the risk of vascular related dementia.

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.

Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra-tumourous thymopoiesis and export of inefficiently tolerized T-cells to the periphery. The autoimmune regulator (AIRE) drives the expression of self-antigens in the thymic medulla and plays an essential role in 'central' tolerance in both humans and mice. However, while inactivating AIRE mutations result in the 'autoimmune polyendocrinopathy syndrome type 1' (APS-1), its major features are not well reproduced in AIRE-knock-out mice. Therefore, alternative human disease scenarios with concomitant AIRE deficiency may be valuable tools to test conclusions drawn from mouse models. Here we show, in a large series, that approximately 95% of thymoma patients are 'chimeric'; expression of AIRE and major AIRE-related autoantigens (eg insulin) were undetectable in their tumours but maintained in their remnant thymic tissue and lymph nodes. Notably, despite the AIRE-deficient thymopoiesis in thymomas, disorders and autoantibodies typical of APS-1 were distinctly uncommon in these patients. The one striking similarity was in the recently observed neutralizing anti-type I interferon (IFN) antibodies, which are found at diagnosis in 100% of patients with APS-1 and in approximately 60% of patients with thymomas, as we show here. We conclude that APS-1 type autoantigens must be protected from autoimmunity by mechanisms that do not extend to the muscle autoantigens so frequently targeted in thymoma patients but so rarely recognized in APS-1. Thus our findings argue strongly for a tolerogenic function of AIRE beyond its role in negative T-cell selection in human thymopoiesis, and/or for specific autoimmunization against muscle in thymomas., (Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

There is increasing evidence that obesity and overweight may be related, in part, to adverse work conditions. In particular, the risk of obesity may increase in high-demand, low-control work environments, and for those who work long hours. In addition, obesity may modify the risk for vibration-induced injury and certain occupational musculoskeletal disorders. We hypothesized that obesity may also be a co-risk factor for the development of occupational asthma and cardiovascular disease that and it may modify the worker's response to occupational stress, immune response to chemical exposures, and risk of disease from occupational neurotoxins. We developed 5 conceptual models of the interrelationship of work, obesity, and occupational safety and health and highlighted the ethical, legal, and social issues related to fuller consideration of obesity's role in occupational health and safety.

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.

Unlabelled: Thyroid volume measurement by ultrasonography (US) is essential in numerous clinical diagnostic and therapeutic fields. While known to be limited, the accuracy and precision of two-dimensional (2D) US thyroid volume measurement have not been thoroughly characterized., Objective: We sought to assess the intra- and interobserver variability, accuracy and precision of thyroid volume determination by conventional 2D US in healthy adults using reference volumes determined by three-dimensional (3D) US. Design,, Methods: In a prospective blinded trial, thyroid volumes of ten volunteers were determined repeatedly by nine experienced sonographers using conventional 2D US (ellipsoid model). The values obtained were statistically compared to the so-called true volumes determined by 3D US (multiplanar approximation), the so-called gold standard, to estimate systematic errors and relative deviations of individual observers., Results: The standard error of measurement (SEM) for one observer and successive measurements (intraobserver variability), was 14%, and for different observers and repeated measurements (interobserver variability), 17%. The minimum relative thyroid volume change significantly different at the 95% level was 39% for the same observer and 46% for different observers. Regarding accuracy, the mean value of the differences showed a significant thyroid volume overestimation (17%, p < 0.01) by 2D relative to 3D US., Conclusion: 2D US is appropriate for routine thyroid volumetry. Nevertheless, the so-called human factor (random error) should be kept in mind and correction is needed for methodical bias (systematic error). Further efforts are required to improve the accuracy and precision of 2D US thyroid volumetry by optimizing the underlying geometrical modeling or by the application of 3D US.

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.

Background: Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined., Objective: To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA., Methods: Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes., Results: No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01)., Conclusions: Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.

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.

Unlabelled: 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.

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.

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.

A novel thyroid ultrasound phantom with tissue-equivalent characteristics was designed consisting of two lobes with three lesions each. One set of lesions is manufactured with a -5 dB echo difference to the surrounding tissue, the other with -10 dB. This phantom was used as a standardized measuring object for reproducibility of two-dimensional and three-dimensional ultrasound volumetry and for an interobserver and intraobserver variability study. For the variability study, nine experienced physicians scanned all specimen three times. Each time the volumes were calculated using the ellipsoid method. A three-dimensional ultrasound scan of each specimen was performed to evaluate all volumes by multiplanar volume approximation. The results of these volume data were compared to the known true volumes. The interobserver variability ranged from -13.4% to 11.9% (median, 0.7%); the intraobserver variability from -9.1% to 16.4% (median, 3.6%). The systematic error as calculated from the total mean of all specimens is 0.5% for the interobserver variability and 4.1% for the intraobserver variability. The phantom can be used for training purposes, to improve the skills of the examining physicians by simulating real thyroid morphology, to provide a standardized reference object for long-term quality control of conventional ultrasound scanners, and the determination of the accuracy and reproducibility of volumetry using three-dimensional ultrasound systems.