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Unlabelled: T stage was redefined for patients with differentiated thyroid carcinoma (DTC) between the 5th and 7th versions of the UICC tumour classification system., Patients, Methods: 636 patients (486 women, 150 men; mean age 49.1 ± 15.6 years, mean follow-up 4.6 years) who had been treated with ablative radioiodine therapy after thyroidectomy for papillary (PTC) or follicular thyroid carcinomas (FTC) were retrospectively assessed on occurrence of locoregional recurrent disease, or cervical lymph node or distant metastases. Disease-free survival was calculated from initial T stage, classified according to both versions of the UICC staging system and compared with the prognostic value of primary tumour size. Kaplan-Meier method and two measures of explained variation, (1) R2 based on the (partial) likelihood ratio statistic of the Cox proportional hazards model and (2) a model-free variant of a distance measure proposed by Schemper had the aim to detect the most advantageous classification., Results: Of the 508 patients with PTC, 11 (2.2%) developed a local recurrence, 37 (7.3%) cervical lymph node and 23 (4.5%) distant metastases, 3 (2.3%), 8 (6.3%), and 18 (14.1%) were the numbers for the 128 FTC patients respectively. The two classification systems yielded an equal count of statistically significant differences regarding disease-free survival in patients with PTC while UICC 7th classification appeared slightly advantageous in patients with FTC. Regarding explained variation the UICC 7th classification tended to be superior to the UICC 5th classification, both in PTC and FTC, however statistical significance was not reached., Conclusion: The primary tumour size significantly added to the prognosis regarding local cervical and distant metastases.

The recommended target dose in radioiodine therapy of solitary hyperfunctioning thyroid nodules is 300-400Gy and therefore higher than in other radiotherapies. This is due to the fact that an unknown, yet significant portion of the activity is stored in extranodular areas but is neglected in the calculatory dosimetry. We investigate the feasibility of determining the ratio of nodular and extranodular activity concentrations (uptakes) from post-therapeutically acquired planar scintigrams with Monte Carlo simulations in GATE. The geometry of a gamma camera with a high energy collimator was emulated in GATE (Version 5). A geometrical thyroid-neck phantom (GP) and the ICRP reference voxel phantoms "Adult Female" (AF, 16ml thyroid) and "Adult Male" (AM, 19ml thyroid) were used as source regions. Nodules of 1ml and 3ml volume were placed in the phantoms. For each phantom and each nodule 200 scintigraphic acquisitions were simulated. Uptake ratios of nodule and rest of thyroid ranging from 1 to 20 could be created by summation. Quantitative image analysis was performed by investigating the number of simulated counts in regions of interest (ROIs). ROIs were created by perpendicular projection of the phantom onto the camera plane to avoid a user dependant bias. The ratio of count densities in ROIs over the nodule and over the contralateral lobe, which should be least affected by nodular activity, was taken to be the best available measure for the uptake ratios. However, the predefined uptake ratios are underestimated by these count density ratios: For an uptake ratio of 20 the count ratios range from 4.5 (AF, 1ml nodule) to 15.3 (AM, 3ml nodule). Furthermore, the contralateral ROI is more strongly affected by nodular activity than expected: For an uptake ratio of 20 between nodule and rest of thyroid up to 29% of total counts in the ROI over the contralateral lobe are caused by decays in the nodule (AF 3 ml). In the case of the 1ml nodules this effect is smaller: 9-11% (AF) respectively 7-8% (AM). For each phantom, the dependency of count density ratios upon uptake ratios can be modeled well by both linear and quadratic regression (quadratic: r(2)>0.99), yielding sets of parameters which in reverse allow the computation of uptake ratios (and thus dose) from count density ratios. A single regression model obtained by fitting the data of all simulations simultaneously did not provide satisfactory results except for GP, while underestimating the true uptake ratios in AF and overestimating them in AM. The scintigraphic count density ratios depend upon the uptake ratios between nodule and rest of thyroid, upon their volumes, and their respective position in a non-trivial way. Further investigations are required to derive a comprehensive rule to calculate the uptake or dose ratios based on post-therapeutic scintigraphy., (Copyright © 2011. Published by Elsevier GmbH.)

Objective: The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well-defined group of patients with thyroid carcinomas with extrathyroidal extension. The aim of the present study was to evaluate the relationship of the primary tumour size with clinicopathological features as well as the outcome of patients with minimum and extensive extrathyroidal growth (pT3b- and pT4a-tumours; UICC 2002/2003, 6th ed)., Methods: The tumour diameter was available in 324 out of 351 MSDS patients (244 females, 80 males). Mean age of patients was 47.7±12.0 years (range, 20.1-69.8 years), and the median follow-up was 6.2 years. The relationship between primary tumour size and the following clinicopathological data was investigated: age, gender, histological tumour type (papillary thyroid carcinomas (PTC) versus follicular thyroid carcinomas (FTC)) and UICC/AJCC TNM classification. In addition, the correlation between primary tumour size and event-free and overall survival was assessed., Results: The FTC of our series were significantly larger than PTC (3.46 vs 1.84 cm; P<0.001). Patients suffering from pT3b-tumours presented with significantly smaller tumour size than those with extensive extrathyroidal growth (pT4a-tumours) (1.9 vs 3.0 cm; P<0.01). All patients with distant metastases suffered from tumours >2 cm. Furthermore, event-free and overall survival were significantly correlated with increasing tumour size (P<0.05). Using multivariate analysis, a pT4a-category and a tumour diameter >2 cm remained independent predictors of survival., Conclusions: In patients suffering from differentiated thyroid carcinoma with extrathyroidal growth (pT3b and pT4a), the tumour size is an independent predictor of event-free and overall survival.

Unlabelled: The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well defined group of patients with locally aggressive thyroid carcinomas (pT4; AJCC/UICC 1997). The aim of the present study was to compare the survival of patients with minimum and extensive extrathyroidal growth according to the new AJCC/UICC TNM staging system 2009., Patients, Methods: The follow-up data of 347 patients were analysed. Patients were reclassified according to the current AJCC/UICC 2009 classification. The event-free and overall survival was evaluated using Kaplan-Meier analysis. In addition, postoperative complications and status of disease were documented., Results: 327 patients were assigned to stage pT3 and 20 patients to stage pT4a, respectively. Median follow-up was 6.1 years (range 0.04-9.8 years). 92.5% of patients reached complete remission. There were 7.8 % recurrences in the thyroid bed, in locoregional lymph nodes and/or in distant sites. The overall survival was >98% both in pT3 and pT4a patients (p = n. s.). In contrast, the event-free survival was significantly less favourable in pT4a patients (p < 0.001). Using multivariate analysis the following parameters were significant predictors of event-free survival: histological tumour type, degree of extrathyroidal extension and nodal metastasis (p < 0.05)., Conclusions: The MSDS patients with locally aggressive differentiated thyroid cancer showed an excellent overall survival during a median follow-up of 6.1 years. According to the current AJCC/UICC 2009 classification, pT3 patients with minimal extrathyroidal extension revealed a significantly better event-free survival than pT4a patients with extensive extrathyroidal growth.

Unlabelled: The primary aim of this study was to compare pharmacoeconomic effects of hypothyroidism secondary to hormone withdrawal (THW) and recombinant human TSH (rhTSH) for follow-up WBS in patients with differentiated thyroid cancer (DTC). The second aim was to determine patients' preference for one procedure or the other., Patients, Methods: This retrospective survey included 327 patients with DTC who underwent at least one in-hospital WBS with rhTSH between 1999 and 2006. They had also undergone THW for WBS. Patients received a two-page questionnaire via mail addressing five symptoms and ten items regarding managing their daily life which was answered by 61.6%. The responder group did not differ from the entire group. The medical and societal cost of both procedures for diagnostic WBS was calculated including direct and all ascertainable indirect cost for the reference year 2005. A sensitivity analysis included the German DRG system of 2007 and 2010., Results: After THW, 94% of patients reported hypothyroid symptoms. Using rhTSH, symptoms occurred significantly less. As a result, 97% of patients favored rhTSH over THW. Mean absence from salaried work was 12.3 days after THW compared to 4 days with rhTSH. Family members of salaried employees missed 3 and 0.7 workdays after THW and rhTSH, respectively. Almost twice as often, medical attention was sought after THW (36%) compared to rhTSH (19 %). Undergoing THW, 48% of patients still used their car while hypothyroid. Our cost calculation revealed a slight benefit of about 89.00 Euro in favour of rhTSH stimulation., Conclusion: Hypothyroidism after THW causes significant morbidity and safety risks. The clinical and societal benefits associated with rhTSH are roughly gained at equivalent overall cost to that of THW.

In spite of the fact that the German Society of Endocrinology has recommended calcitonin as screening-parameter the majority of physicians in Germany do not routinely use calcitonin in patients with thyroid nodules to exclude medullary thyroid cancer (MTC). The future revision of the recommendation should describe reference values for each commercially available assay, separately for men and women (basal and after pentagastrin-stimulation), and should define sonomorphological inclusion criteria. The epidemiological database of the prevalence of MTC is controversial and the specificity of basal elevated calcitonin levels is limited up to the 5-fold of the upper reference level. If renal insufficiency, bacterial infection, and an alcohol- or drug-induced stimulation of calcitonin is excluded, hypercalcitoninaemia should be confirmed by a second measurement (if necessary using another assay). Stimulation of calcitonin by use of pentagastrin is mandatory prior to the decision on thyroidectomy. A stimulated calcitonin level < 100 pg/ml justifies "wait and see". If stimulated calcitonin levels range between 100 and 200 pg/ml or higher, the differentiation between C-cell hyperplasia and MTC remains uncertain, especially in men. The implementation of calcitonin-screening requires the definition of sonographic inclusion criteria and validation of each assay. Additional pre-requisites are excellent logistic (short period between blood sampling and start of the laboratory test), knowledge of differential diagnoses, knowledge of the consumption of drugs and alcohol, availability of pentagastrin-testing and of moleculargenetic testing with full information to the patients and sufficient time before the decision on surgery is made. All this and the choice of a skilled surgeon, experienced in thyroidectomy and lymphadenectomy with a low rate of local complications are the rationale to recommend calcitonin-screening primarily in centers for thyroid disorders.

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.

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.

A 66-year-old woman underwent total thyroidectomy for papillary thyroid carcinoma stage pT4 followed by radioiodine therapy with 3.7 GBq (100 mCi) iodine-131. Radioiodine therapy revealed intense radioiodine uptake of the neck, which was interpreted as thyroid remnant tissue. Follow-up whole-body scans with iodine-131 in hypothyroidism 3 months and 1 year after radioiodine therapy revealed focal uptake in the neck. Computed tomography and gadolinium-enhanced MRI of the neck demonstrated an ovoid lesion in the larynx without gadolinium enhancement. Neither thyroid remnant tissue nor enlarged cervical lymph nodes could be demonstrated either on CT or on MRI. Further examination of the patient in the ear, nose and throat department confirmed the finding of a laryngocele and biopsies demonstrated benign tissue. Follow-up whole-body scans with iodine-131 in hypothyroidism 3 years and after injection of rhTSH 5 years after radioiodine therapy reproduced the focal uptake in the neck. After initial radioiodine therapy thyroglobulin levels were never measurable, not at any of the whole-body scans in hypothyroidism, after rhTSH, or at intermediate follow-up examinations under TSH-suppressive levothyroxine therapy. The patient declined definitive operative revision of the laryngocele and is in good health 8 years after the diagnosis of papillary thyroid carcinoma.

Aim: The apoptotic and necrotic dose-response of thyroid carcinoma cells following irradiation with I was evaluated., Methods: In our in-vitro model, cells of well-differentiated papillary thyroid carcinoma (B-CPAP) were incubated with increasing activity concentrations of I for 2 days. Changes in cell viability and the extents of necrosis and apoptosis were evaluated both immediately and 2 days after irradiation., Results: Viability of B-CPAP cells diminished with increasing I activity concentration. No apoptosis was detectable immediately after irradiation. Two days after irradiation significant apoptosis was found. The lowest I activity concentration at which apoptosis was detectable corresponds to about 1 MBq . ml. At higher activity concentrations a larger percentage of cells became apoptotic but the proportion decreased again at activity concentrations >10 MBq . ml. Likewise, necrosis was minimal at low activity concentrations and showed an exponential increase with rising I activity concentrations (>5-10 MBq . ml). Necrosis was already detectable immediately after irradiation and was the predominant form of cell death at high activity concentrations., Conclusion: The data suggest that the nature of the cytotoxic effect of I and whether it leads to apoptotic or necrotic cell death is dose-dependent. High I doses seem to produce mainly necrotic phenomena, whereas at low I activity concentrations apoptotic phenomena prevail. The predominance of delayed apoptosis could explain why radioiodine therapy at lower doses is often linked to delayed onset and possible continuation of thyroid volume reduction over some months and even up to a year.

Unlabelled: The incidentally detected thyroid nodule using sonography is described as incidentaloma; the most nodules have a diameter up to 1.5 cm. Sonography will detect thyroid nodules in more than 20% of the population in Germany. Epidemiological studies investigating the prevalence of malignancy in such incidentalomas are missing. The incidence of differentiated thyroid cancer is about 3 per 100,000 people and year. However, several monocentric studies have shown a prevalence of malignancy of up to 10% of the thyroid nodules in selected patients' group. The histology did notfound microcarcinomas only, but also small cancer with infiltration of the thyroid capsule, lymph node metastasis or multifocal spread. The studies were not designed for outcome measurement after early and incidental detection of small thyroid cancers. Hypoechogenity, ill defined borders, central hypervascularization or microcalcifications were used as combined criteria for risk stratification. The second method for risk stratification is scintigraphy and further tests are warranted for hypofunctioning nodule > or =1 cm. Additionally, the family history, patient's age <20 years, former radiation of the neck, and measurement of calcitonin should be regarded. Without such a risk stratification selection for fine needle aspiration is impossible. Fine needle aspiration of non-palpable incidentalomas led to non-representative or unequivocal cytological findings in up to 40%. Because better outcome of incidentally detected small thyroid carcinomas is not proved and because sonography, scintigraphy and fine needle aspiration remain imprecise regarding dignity of incidentalomas, fine needle aspiration is not the standard for small, non-palpable thyroid nodules., Conclusion: For management of incidentaloma, sonographically unsuspicious, scintigraphically indifferent (nodules > or =1 cm) and without any risk factors in patients' history, wait and see is justified when patient is informed about the problem.

Background: The extent of thyroid resection and the necessity of lymph node dissection has become an issue of controversy in patients with incidental multifocal papillary microcarcinoma., Method: Between 1993 and 2001 a total of 4120 patients underwent surgery for thyroid diseases: 142 patients showed papillary thyroid cancer of < or = 1 cm, multifocal microcarcinomas were found in 22 patients (15.5%). Twenty patients (17 women, three men, aged 26-71 years) met the inclusion criterion of having pre- and intraoperatively no indication of malignancy (incidentaloma). A limited surgical procedure ranging from bilateral subtotal (n=15), ipsilateral total, contralateral subtotal (n=4) to bilateral total (n=1) thyroidectomy without lymph node dissection was performed. The mean volume of thyroid remnants was 4.3 ml., Results: In 16/20 (80%) patients, the thyroid remnant was ablated by the first dose of 131I, using 3.7 GBq 131I in 15 patients and 1.85 GBq 131I in one patient. Three patients received a second, and one patient a third radioiodine ablation. All 20 patients remained free from relapse or metastasis, documented by negative 131I whole-body scintigraphy and unmeasurable thyroglobulin levels after thyroid hormone withdrawal in hypothyroidism. One patient died 7 years after the diagnosis of thyroid cancer from primary lung cancer. Median follow-up was 65 months (range, 24-120 months)., Conclusion: Subtotal thyroidectomy followed by radioiodine therapy without completion thyroidectomy and lymphadenectomy is a possible option in incidental multifocal microcarcinomas.

The procedure guidelines for radioiodine therapy (RIT) of differentiated thyroid cancer (version 2) are the counter-part to the procedure guidelines for (131)I whole-body scintigraphy (version 2) and specify the interdisciplinary guidelines for thyroid cancer of the Deutsche Krebsgesellschaft and the Deutsche Gesellschaft für Chirurgie concerning the nuclear medicine part. Compared with version 1 facultative options for RIT can be chosen in special cases: ablative RIT for papillary microcarcinoma

Papillary thyroid microcarcinomas

The version 2 of the procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer is an update of the procedure guideline published in 1999. The following statements are added or modified: The two alternatives of an endogenous TSH-stimulation by the withdrawal of the thyroidal hormone medication and of an exogenous TSH-stimulation by the injection of the recombinant human TSH (rhTSH) have an equal sensitivity for the diagnostic use of radioiodine and for the measurement of thyroglobulin. Image acquisition under rhTSH is obtained approximately 48 h after the radioiodine administration, while an interval of about 72 h is preferred under endogenous TSH-stimulation. If iodine-negative metastases are expected, the feasibility of scintigraphy using (99m)Tc sestamibi or preferably positron emission tomography using (18)F-fluorodeoxyglucose should be considered. The sensitivity of FDG-PET is increased by TSH-stimulation. Before planning the iodine-131 scintigraphy the patient has to avoid iodine-containing medication and the possibility of additives of iodine in vitamin- and electrolyte-supplementation has to be considered.

Background: The growth and spread of many tumors are triggered by changes in cell membrane metabolism, which can lead to systemic alterations in levels of phospholipids. We sought to determine whether plasma levels of several phospholipids could differentiate between healthy remnants of thyroid tissue and residual tumor tissue or metastases in patients with thyroid carcinoma., Methods: We measured plasma phospholipid levels by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in blood samples from 30 patients with thyroid cancer who had been rendered hypothyroid in preparation for diagnostic or therapeutic administration of iodine-131. All patients had undergone total thyroidectomy. Iodine-131 whole-body scintigraphy and measurements of thyroglobulin values during up to 3 years of follow-up were used to distinguish patients in remission from those with only healthy thyroid remnants and those with tumor tissue or metastases., Results: Mean (+/- SD) levels of sphingomyelin (0.33 +/- 0.06 mmol/L vs. 0.46 +/- 0.03 mmol/L, P <0.0001) and phosphatidylcholine (1.34 +/- 0.19 mmol/L vs. 2.15 +/- 0.33 mmol/L, P <0.0001) were significantly lower in patients with metastatic thyroid cancer (n = 8) than in patients (n = 12) who were in remission. Patients with only remnants of thyroid tissue (n = 10) also had significantly lower phospholipid levels than did patients in remission, but significantly greater levels that did patients with tumor tissue or metastases., Conclusion: These preliminary results suggest that 31P-MRS may be useful in helping to differentiate the presence of tumor tissue, remnants of thyroid tissue not requiring further treatment, and remission in patients with thyroid cancer.

Aim: The change of both amount and chemical forms of radioiodine exhaled in the air of rooms with patients on the therapy ward should be investigated depending on radioactivity applied, time after application, and kind of thyroid disease., Methods: The air of ward-rooms of 62 patients with thyroid carcinoma, Graves' Disease, and autonomy which received different therapy doses, was investigated with an portable constant air flow sampler. Different chemical iodine species (organic, elemental, aerosol bound) were collected during 8 hr in various filters until 3 days after application of the radioiodine capsule, according to their chemical form. The radioactivity in the filters was measured with a well counter on defined time points after application., Results: The radioactivity exhaled was between 0.008 and 0.03% related to activity of radioiodine applied. The percentage of radioiodine exhaled related to the activity applied, differed significantly depending on disease and changed as follows: Grave's Disease > autonomy > carcinoma. The exhalation of radioiodine became stronger with increasing applied activities and showed an exponential decrease with time. The most part of radioiodine was present in organic bound form. This organic portion decreased with time in favour of the other iodine species., Conclusion: The degree of accumulation of radioiodine orally applied within thyroid seems to be in direct proportion to the extend of its exhalation. Further measurements directly in the breathing air of RIT-patients are necessary, in order to clarify the relationship between degree of thyroid uptake and quantity as well as chemical form of radioiodine exhaled.

The radioablation of thyroid remnants improves the prognosis of differentiated thyroid cancer. In our prospective study an activity of 3.7 GBq 131I failed to completely ablate the remnants in 46 out of 101 patients, but a 3-year follow-up period was uneventful. One other patient had a recurrence early after thyroidectomy. In view of possible stunning effects of 131I it might be advantageous to visualize such remnants by imaging modalities which do not emit beta-particles. Our data have revealed that neither magnetic resonance imaging (MRI), nor ultrasonography (US), nor 99Tcm-sestamibi scintigraphy, nor positron emission tomography could detect or reliably exclude minimal remnants. Such remnants did not produce thyroglobulin (Tg). A 123I and 131I uptake of> 10% after thyroidectomy was associated with about a 90% probability of persistent remnants. On the other hand, MRI was helpful in the patient group (n = 32) with Tg>4ng x ml(-1) at the second whole-body scintigraphy (TSH>30 mU x l(-1)) for planning the management of lymph node metastases (n = 15 patients): 12 patients had subsequent surgery and three patients radioiodine therapy. We recommend that MRI be used early in follow-up care when Tg is elevated. The decision of whether or not to treat persistent thyroid remnants should not be made on the basis of MRI, US or nonspecific scintigraphic methods. Complete ablation did not appear to have any clinical benefit in our study group.

In this study in-vitro (31)P high-resolution NMR spectroscopy of human blood plasma was optimized to obtain absolute concentrations of the major plasmaphospholipids: phosphatidylethanolamine plus sphingomyelin (PE + SM), 1- and 2-acyl-lysophosphatidylcholine (LPC1 and LPC2), phosphatidylinositol (PI) and phosphatidylcholine (PC). Plasma spectra of 33 patients with thyroid carcinoma were acquired at 121.49 MHz using a 300 MHz spectrometer. The patients were rendered hypothyroid (TSH >30 mU/l) in preparation for a whole-body scintigraphy. The whole-body scintigraphy showed tumour tissue or metastases in 16 patients (group C). Owing to an inconclusive whole-body scintigraphy, 17 patients were classified as being in remission (group B). After levothyroxine substitution 14 patients of group B were measured in euthyroidism too (group D). Besides these sub-groups, there was a control group made up of 23 healthy volunteers (group A). Group B showed significantly higher PE + SM and PC concentrations than group C (0.59 +/- 0.02 mmol/l PE + SM in B vs 0.48 +/- 0.02 mmol/l in C; 2.1 +/- 0.1 mmol/l PC in B vs 1.6 +/- 0.1 mmol/l in C). In comparison with group D higher concentrations of the phospholipids PE + SM and PC as well as PI were found in group B (0.59 +/- 0.02 mmol/l PE + SM in B vs 0.48 +/- 0.03 mmol/l in D; 0.074 +/- 0.005 mmol/l PI in B vs 0.046 +/- 0.004 mmol/l in D; 2.1 +/- 0.1 mmol/l PC in B vs 1.6 +/- 0.1 mmol/l in D). The data indicate that under the condition of hypothyroidism only patients in remission (group B) show significantly increased phospholipid concentrations, whereas the values in patients with remaining tumour tissue (group C) do not differ from those of the reference groups A and D. This finding is interpreted as an interference between the hormonal status and the systemic effects of cancer., (Copyright 2000 John Wiley & Sons, Ltd.)

The radiolabeled glucose analogue F-18-Fluoro-Deoxyglucose (F-18-FDG) and Positron Emission Tomography (PET) were used to measure glucose metabolism of the thyroid in vivo. We evaluated patients with autonomous goitre before therapy with radioiodine in comparison to patients with normal thyroids. 30 patients with autonomous goitre underwent scanning the day before radioiodine therapy. 19 patients with head or brain tumours and normal thyroids were the controls. Overall F-18-FDG uptake was determined for all thyroids and proved to be significantly higher in autonomy patients compared to controls and in disseminated autonomous goitre slightly but not significantly higher than in focal autonomy. In autonomy patients F-18-FDG uptake increased with increasing radioiodine uptake and shorter radioiodine half-life. These results indicate that glucose metabolism is enhanced in the thyroids of patients with focal and disseminated autonomy. The negative correlation of radioiodine half-life and glucose metabolism as well as the positive correlation of radioiodine uptake and glucose metabolism suggest connections of glucose metabolism and iodine-dependent hormone synthesis in thyroid cells.

Aim: Gain-of-function mutations of the thyrotropin receptor (TSHR) gene have been invoked as one of the major causes of toxic thyroid adenomas. This study evaluates F-18-FDG-PET in these patients., Methods: Twenty patients with focal autonomous nodules and ten with disseminated autonomy were investigated the day before radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls., Results: F-18-FDG-Uptake was higher in patients than in controls. Focal autonomous nodules were associated with focally enhanced glucose metabolism. Disseminated autonomous goiters showed various patterns of focal or global hypermetabolism., Conclusion: Autonomous thyroid tissue caused by constitutive mutations of the TSH receptor is characterised by simultaneous increases in glucose and iodine metabolism which are correlated.

Aim: FDG-PET and MIBI-scintigraphy with SPECT were compared to [131I]-whole-body scintigraphy (WBS) and morphologic imaging in the follow-up of differentiated thyroid cancer. Their influence of therapy-planning was analysed., Methods: In 50 consecutive patients (papillary/ follicular/variants of a follicular carcinoma: 33/13/4; primary status: pT1/2/3/4: 3/16/9/22) FDG-PET of neck/chest and MIBI-whole-body scan including SPECT were performed during hypothyreosis and before WBS. Morphologic imaging was done by MRI in all and by CT of the lung without contrast media in 21 patients., Results: The complete extent of metastases was detected by FDG-PET in 11 and by MIBI-scintigraphy also in 11 of 22 patients with evidence of disease. The combined evaluation of WBS and FDG-PET as well as of WBS and MIBI-scintigraphy held true in 18 of 22 patients. Limiting FDG-PET or MIBI-scintigraphy to patients with elevated thyroglobulin (Tg)-levels and negative WBS only, would not, therefore, alter the sensitivity of this algorithm. The diagnostic benefit of FDG-PET and MIBI-scintigraphy was confined to lymph node metastases. The 1 cm limit for lymph node size in morphologically based imaging did not apply to FDG-PET and MIBI-scintigraphy. None of the 6 patients with small (< 1 cm) pulmonary metastases showed either FDG- or MIBI-uptake, but could be diagnosed by spiral-CT., Conclusion: WBS cannot be replaced by FDG-PET or MIBI-scintigraphy; neither of the latter was better than the other. Rising Tg-levels, negative WBS and the exclusion of pulmonary metastases by spiral-CT define the constellation in which FDG-PET and MIBI-scintigraphy can provide data of therapeutic relevance.

Metastases of differentiated thyroid cancer may show different uptake patterns for fluorine-18 fluorodeoxyglucose and [131I]NaI. FDG positron emission tomography (PET), iodine-131 whole-body scintigraphy (131I WBS) and magnetic resonance imaging were performed in 58 unselected patients, and spiral computed tomography (CT) of the lung in 25 patients. Thirty-eight patients presented with papillary carcinomas, 15 patients with follicular carcinomas and five patients with variants of follicular carcinoma. Primary tumour stage (pT) was pT1 in 3, pT2 in 19, pT3 in 11 and pT4 in 25 cases. For the detection of metastases, FDG PET was found to have a sensitivity of 50%, 131I WBS a sensitivity of 61%, and the two methods combined a sensitivity of 86%. When FDG PET was limited to patients with elevated thyroglobulin (Tg) levels and negative 131I WBS, the sensitivity of this algorithm was 82%. Of the 21 patients with lymph node metastases, seven presented with FDG uptake but no iodine uptake. In four of them, a second FDG hot spot appeared in a lymph node metastasis of normal size. Five of the seven patients underwent surgery. None of the eight patients with pulmonary metastases smaller than 1 cm exhibited FDG uptake, while five of them had iodine uptake. All had positive results on spiral CT. In conclusion, FDG PET cannot be substituted for 131I WBS. If the Tg level is elevated and 131I WBS is negative, FDG PET can be used to detect lymph node metastases and complements anatomical imaging. A spiral CT of the lung is useful to exclude pulmonary metastases before planning a dissection of iodine-negative lymph node metastases.

The current level of knowledge about radioiodine therapy (RITh) for well-differentiated thyroid carcinoma under consideration of the recent literature is summarised. In RITh for thyroid carcinoma two major fields can be distinguished: the ablation of the thyroid remnant and the therapy of recurrences resp. local and distant metastases. New large American studies indicate, that the prophylactic post operative ablation of the thyroid remnant in primary tumours over 1.5 cm in diameter is linked with a distinct improvement of the long-term prognosis. The RITh is effective also in distant metastases, if applied early, when the tumour volume is still small. The prerequisite is an appropriate follow-up. Surveys about the application of RITh for well-differentiated thyroid carcinoma in Europe and in the USA reveal that uniform treatment recommendations designed to conform interdisciplinary demands are urgently required.

Aim: In 76 patients with thyroid carcinoma (60 f., 16 m.; age 51 +/- 15 years; 52 with papillary, 22 with follicular, 2 with Hürthle cell thyroid carcinoma), three different schemes to withdraw LT4 before 131I whole body scintigraphy were compared., Method: In scheme I no interval LT3 medication is applied. Scheme II starts one week after withdrawal of LT4 with a two weeks lasting LT3 medication: 40-80 micrograms LT3/die in the first week and 20 micrograms LT3/die in the second week. Afterwards no further LT3 medication is given. Scheme III is identical to scheme II in the first three weeks but 20 micrograms LT3 medication is continued until 131I-application. Retrospectively 121 studies were evaluated concerning the scheme specific increase of TSH. Factors which may influence the increase of TSH were analysed, i.e. age, sex, thyreoglobuline, LT4 dose, duration of LT4 treatment, histological type of carcinoma, result of 131I whole body scanning., Results: There was a significant relation between increase of TSH and the applied scheme. Schemes with interval LT3 medication are more comfortable for the patient but time to stimulate TSH to values > or = 30 microIU/ml is prolonged, especially using scheme III. Female patients needed a significantly longer time compared to male patients to reach a TSH value > or = 30 microIE/ml. Concerning repetitive withdrawal of LT4, there was a fair intraindividual reproducibility of the time period from LT4 withdrawal to TSH values > or = 30 microIE/ml., Conclusion: Every scheme has its specific field of indication depending on the compliance of the patients.

Treatment with 131I is a well known and widely accepted therapy for benign thyroid disease and thyroid cancer. High dose 131I therapy for ablative reasons in well-differentiated thyroid cancer is done mostly in hospitals with controlled area and adequate equipment for radiation protection. Low-dose therapies, however, of hyperthyroidism, thyroid autonomy and goiter may be done in out-patients in many countries. Limits of radioactivity administered for an ambulant therapy are varying. In Germany, 131I therapy of out-patients is generally not permitted. As many patients are waiting for a therapy but capacity is too low, waiting lists up to several months exist. This leads to a kind of medical tourism into other countries where therapy of out-patients is possible. This is a crucial point with regard to optimal medical care as well to health economics. This paper presents the results of a questionnaire which was sent to the national EANM delegates of all European countries. There is a great variability among these countries which indicates the different views handling of radioactivity and radiation protection. A more detailed questionnaire about regulatory and administrative rules initiated by an EANM task group for risk assessment in nuclear medicine is on the way.

In 62 patients with thyroid carcinoma 79 MRI bone marrow examinations and 48 bone marrow scintigraphies were recorded before or following radioiodine therapy, to study the extent of bone marrow expansion. The results of both methods were the same. In 34/79 investigations normal findings were seen, in 18 the bone marrow expanded to the middle third and in 26 to the distal third of the femur. One patient showed bone marrow expansion to the tibia. These results were compared with the following data: histology of tumor, TNM-staging, time passed since thyroidectomy, accumulated doses of radioiodine therapy, results of 131I scintigraphy, hematological changes, thyroglobulin level, age and sex. No significant correlations were found between these and the bone marrow imaging results. Bone marrow changes in patients before radioiodine therapy were similar to those in patients treated with up to 48 GBq 131I. Blind biopsy of the posterior iliac crest in five patients showed slightly pathological reactive changes. In only 2/17 follow-up studies an increase of bone marrow expansion was seen. In 8 patients localized findings indicating malignant infiltration were observed. In 4/8 patients metastases of thyroid carcinoma were known or confirmed by pathological radioiodine uptake and in 2/8 metastatic involvement was assumed because of an increased thyroglobulin level.

Thyroid carcinoma is not a common disorder but the metastatic thyroid carcinoma manifesting thyrotoxicosis is exceedingly rare. Since Leiter et al. described the first patient with adenocarcinoma of the thyroid with functioning metastases and postoperative thyrotoxicosis in 1946, about 20 such cases have been reported. We have examined two cases of metastatic follicular thyroid carcinoma with T3-hyperthyroidism after surgical ablation of the gland. The thyrotoxicosis was induced by excessive iodine contamination during preoperative radiological examination.