[Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 3)]. / Verfahrensanweisung zur Radioiodtherapie (RIT) beim differenzierten Schilddrüsenkarzinom (Version 3).

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.

[Guideline for radioiodine therapy for benign thyroid diseases (version 4)]. / Leitlinie zur Radioiodtherapie (RIT) bei benignen Schilddrüsenerkrankungen (Version 4).

Version 4 of the guideline for radioiodine therapy for benign thyroid diseases includes an interdisciplinary consensus on decision making for antithyroid drugs, surgical treatment and radioiodine therapy. The quantitative description of a specific goiter volume for radioiodine therapy or operation was cancelled. For patients with nodular goiter with or without autonomy, manifold circumstances are in favor of surgery (suspicion on malignancy, large cystic nodules, mediastinal goiter, severe compression of the trachea) or in favor of radioiodine therapy (treatment of autonomy, age of patient, co-morbidity, history of prior subtotal thyroidectomy, profession like teacher, speaker or singer). For patients with Graves' disease, radioiodine therapy or surgery are recommended in the constellation of high risk of relapse (first-line therapy), persistence of hyperthyroidism or relapse of hyperthyroidism. After counseling, the patient gives informed consent to the preferred therapy. The period after radioiodine therapy of benign disorders until conception of at least four months was adapted to the European recommendation.

Intra- and interobserver variability of thyroid volume measurements in healthy adults by 2D versus 3D ultrasound.

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.

[Radiation exposure in (90)Y-Zevalin therapy: results of a prospective multicentre trial]. / Strahlenexposition bei der (90)Y-Zevalin-Therapie: Ergebnisse einer prospektiven multizentrischen Studie.

UNLABELLED: AIM of this study was the assessment of the radiation exposure from preparation and application of (90)Y-Zevalin, the measurement of the dose rate at the patient, the exposure of family members as well as the determination of the activity concentration in urine of patients. METHODS: Overall data from 31 therapeutic administrations carried out in four institutions were evaluated. During preparation and application of (90)Y-Zevalin the finger exposures of radiochemists, technicians, and physicians were measured. The dose rate of the patient was measured immediately after radioimmunotherapy. In patients treated in a nuclear medicine therapy unit, urine was collected over a two day period and the corresponding activity was determined. Family members of outpatients were asked to wear a dosimeter over a seven day period. RESULTS: During the preparation we found a maximum skin dose of 6 mSv at the average, and during application of 3 mSv, respectively. After administration of (90)Y the dose rate was 0.4 +/- 0.1 microSv/h at 2 m distance. Urine measurements yielded a cumulated 24 h excretion of 3.9 +/- 1.4% and 4.4 +/- 1.4% within 48 h, respectively, that is equivalent to 43 +/- 18 and 50 +/- 20 MBq of (90)Y, respectively. Family members received a radiation exposure of 40 +/- 14 microSv over seven days. CONCLUSION: During preparation and application of (90)Y-Zevalin appropriate radiation shielding is necessary. For family members as well as nursing staff no additional special radiation protection measures beyond those being common for other nuclear medicine procedures are necessary.

A novel thyroid phantom for ultrasound volumetry: determination of intraobserver and interobserver variability.

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.

[Intrathyroidal iodine concentration after application of non-ionic contrast media with and without prophylactic application of perchlorate]. / Intrathyreoidale Iodkonzentration nach Applikation nichtionischer Kontrastmittel ohne und mit Perchlorat-Gabe.

AIM: This study was designed to show the effect of a nonionic contrast medium (Iomeprol-300; CM) on the intrathyroidal iodine concentration with and without a concomitant medication with perchlorate (1380 mg/d) to block the thyroidal iodine uptake. VOLUNTEERS AND METHODS: Twelve volunteers recieved 100 ml Iomeprol-300 intravenously and the perchlorate prophylaxis mentioned above. Another 12 volunteers got 100 ml Iomeprol-300 only. By means of X-ray-fluorescence-analysis the intrathyroidal iodine concentration was determined in advance as well as 0.2, 1, 3, 5, 7, 24, 48, 72, and 96 hours after the application of the CM. RESULTS, CONCLUSION: The intrathyroidal iodine concentration did not change in the group of volunteers on perchlorate medication. Without perchlorate the intrathyroidal iodine concentration decreased after the application of the CM when it was initially high (722 +/- 66 microg/ml before, 670 +/- 65 microg/ml after CM; p = 0.046) and increased in case of a low initial concentration (327 +/- 40 microg/ml before, 381 +/- 25 microg/ml after CM; p = 0.046). The effect is significant but its magnitude is too small to be harmful for a patient with a healthy thyroid. The oral application of 1.4 g/d perchlorate inhibits the thyroidal iodine uptake and the intrathyroidal iodine concentration is unaffected by the application of a CM.

Pilot study for comparison of reticulocyte-micronulei with lymphocyte-micronuclei in human biomonitoring.

Biomonitoring tries to determine the consequences for humans of exposures to environmental or pharmaceutical agents. Different end points have been employed to assess the burden of genomic damage. This is the first report comparing a recently introduced new end point, the reticulocyte-micronuclei analyzed by flow cytometry with the widely used lymphocyte-micronucleus assay, applied to two exposure scenarios leading to enhanced genomic damage. Radioiodine therapy was chosen to represent a short time exposure and hemodialysis treatment in end-stage renal failure was chosen to represent a chronic exposure. The results show that iodine radiation induced measurable genomic damage in the lymphocyte-micronucleus assay as well as in the reticulocyte-micronucleus test. Of two groups of patients under hemodialysis treatment, a reduced genomic damage was found with the lymphocyte-micronucleus test, but not with the reticulocyte-micronucleus test in the group undergoing daily hemodialysis, which removes uremic toxins more efficiently as compared to conventional hemodialysis, the treatment applied in the other group. The limited life-span of reticulocytes may make them less suitable for accumulation of chronic low level damage than lymphocytes. In conclusion, the lymphocyte-micronucleus test may be applicable to more exposure situations (including low chronic exposure), but the reticulocyte-micronucleus assay may be easier to perform in a clinical setting. The latter reflects a more rapid reduction of genomic damage after an acute exposure.

[Guideline for radioiodine therapy for benign thyroid diseases (version 3)]. / Leitlinie zur Radioiodtherapie bei benignen Schilddrüsenerkrankungen (Version 3).

The version 3 of the guideline for radioiodine therapy for benign thyroid diseases presents first of all a revision of the version 2. The chapter indication for radioiodine therapy, surgical treatment or antithyroid drugs bases on an interdisciplinary consensus. The manifold criteria for decision making consider the entity of thyroid disease (autonomy, Graves' disease, goitre, goitre recurrence), the thyroid volume, suspicion of malignancy, cystic nodules, risk of surgery and co-morbidity, history of subtotal thyroidectomy, persistent or recurrent thyrotoxicosis caused by Graves' disease including known risk factors for relapse, compression of the trachea caused by goitre, requirement of direct therapeutic effect as well as the patient's preference. Because often some of these criteria are relevant, the guideline offers the necessary flexibility for individual decisions. Further topics are patients' preparation, counseling, dosage concepts, procedural details, results, side effects and follow-up care. The prophylactic use of glucocorticoids during radioiodine therapy in patients without preexisting ophthalmopathy as well as dosage and duration of glucocorticoid medication in patients with preexisting ophthalmopathy need to be clarified in further studies. The pragmatic recommendations for the combined use of radioiodine and glucocorticoids remained unchanged in the 3rd version.

Impact of parathyroid status and Ca and vitamin-D supplementation on bone mass and muscle-bone relationships in 208 Belarussian children after thyroidectomy because of thyroid carcinoma.

This observational study analyzes Ca-P metabolism and its impact on bone mass accrual and density and the muscle-bone mass/mass relationships in male and female children and adolescents who were parathyroidectomized because of thyroid carcinoma. Two hundred and eight children and adolescents (119 girls and 89 boys) from Gomel city (Belarus) and its rural surroundings were referred to our institution after having undergone total thyroidectomy for the treatment of advanced papillary thyroid cancer. A subgroup of children with demonstrated primary hypoparathyroidism received dihydrotachysterol (AT-10) and/or Ca supplementation. Among routine procedures over a maximum follow-up period of 5 years (average 3.7 years, maximum 8 visits), whole-body scans were taken using dual energy X-ray absorptiometry (DXA) at each visit in order to determine whole-body bone mineral content (TBMC), projected "areal" bone mineral density (TBMD), total lean mass (TLM) and total fat mass (TFM). The average serum Ca, P and AP concentrations over the whole observation period were significantly different between the groups; however, TBMC z-scores for all studied children were statistically similar in all visits. In girls, no between-group differences in height- and weight-controlled TBMC and TBMD or the TBMC/TLM ratio were observed (ANCOVA) and supplementation exerted no effect on these data, suggesting that the total bone mass accrual was not impaired by PTH deficiency in the studied conditions. However, non-supplemented boys showed lower values of the TBMC/TLM ratio than girls, and supplementation normalized these values in direct correlation with the induced improvement in serum P availability to bone. Results indicate that the primary impairment in parathyroid function and bone metabolism indicators in the thyroidectomized children was unrelated to any measurable change in crude bone mass values. However, in boys this condition impaired the TBMC/TLM ratio in such a way that the administered supplementation could normalize it as a function of improved P availability. Girls' skeleton seemed to have been naturally protected against the negative metabolic effect of the studied condition. An estrogen-induced enhancement of the biomechanical impact of muscle contractions on bone mass and structure could not be excluded in this group.

[Monitoring of 131I incorporation in nuclear medicine personnel by self accomplished measurements]. / 131I-Inkorporationsüberwachung in der Nuklearmedizin durch regelmässige Eigenmessung des Personals.

AIM: The personnel in nuclear medicine therapy wards must be monitored according to German guidelines for incorporations of (131)I. A surveillance with the employees measuring themselves similarly to the autonomous contamination survey using hand-foot-clothing monitors is presented as an alternative to the monitoring according to the official guidelines. METHOD: The employees use a dedicated device to measure themselves every working day. The automatic individual positioning of the device ensures reliable and reproducible results. The thyroid dose is determined from the measured time activity curve. The individual values of depth and mass of the thyroid are taken into account for activity measurement and dose evaluation, respectively. RESULTS: The employees measure themselves regularly and utilize the device to check for activities in the thyroid at an early stage after suspected incorporation. The almost complete surveillance permits a dosimetry with slight uncertainty. The determined thyroid doses of all monitored persons average to 0.35 mSv per month. CONCLUSION: The incorporation surveillance by autonomous monitoring allows a more reliable and more precise dosimetry than the monitoring according to the official guidelines. Despite numerous measurements the practice saves time and money as a result of the automation.

[Multivariate analysis of factors influencing the effect of radiosynovectomy]. / Multivariate Analyse der Einflussfaktoren auf die Wirkung der Radiosynoviorthese bei entzündlichen Gelenkerkrankungen.

OBJECTIVE: In this prospective study, the time to remission after Radiosynovectomy (RSV) was analyzed and the influence of age, sex, underlying disease, type of joint, and duration of illness on the success rate of RSV was determined. METHODS: A total number of 57 patients with rheumatoid arthritis (n = 33) and arthrosis (n = 21) with a total number of 130 treated joints (36 knee, 66 small and 28 medium-size joints) were monitored using visual analogue scales (VAS) from one week before RSV up to four to six months after RSV. The patients had to answer 3 times daily for pain intensity of the treated joint. The time until remission was determined according to the Kaplan-Meier survivorship function. The influence of the prognosis parameters on outcome of RSV was determined by multivariate discriminant analysis. RESULTS: After six months, the probability of pain relief of more than 20% amounted to 78% and was significantly dependent on the age of the patient (p = 0.02) and the duration of illness (p = 0.05), however not on sex (p = 0.17), underlying disease (p = 0.23), and type of joint (p = 0.69). CONCLUSION: Irrespective of sex, type of joint and underlying disease, a measurable pain relief can be achieved with RSV in 78% of the patients with synovitis, whereby effectiveness is decreasing with increasing age and progress of illness.

[Aa DICOM based PACS for nuclear medicine]. / Ein DICOM-basiertes PACS für die Nuklearmedizin.

The installation of a Radiology Information System (RIS) connected to a Hospital Information System (HIS) and a Picture Archiving and Communications System (PACS) seems mandatory for a nuclear medicine department in order to guarantee a high patient throughput. With these systems a fast transmission of reports, images to the in- and out-patients' wards and private practitioners is realized. Therefore, since April 2000, at the department of nuclear medicine of the university of Würzburg a completely DICOM based PACS has been implemented in addition to the RIS. With this system a DICOM based workflow is realized throughout the department of nuclear medicine for reporting and archiving. The PACS is connected to six gamma-cameras, a PET scanner, a bone densitometry system and an ultrasound device. The volume of image data archived per month is 4 GByte. Patient demographics are provided to the modalities via DICOM-Worklist. With these PACS components a department specific archive purely based on DICOM can be realized. During the installation process problems occurred mainly because of the complex DICOM standard for nuclear medicine. Related to that is the problem that most of the software implementations still contain bugs or are not adopted to the needs of a nuclear medicine department (particularly for PET). A communication software for the distribution of nuclear medicine reports and images based on techniques used for the worldwide web is currently tested.

Does an individual estimation of halflife improve the results of radioiodine therapy of Graves' disease?

AIM: The impact of our dosimetry concept on radioiodine therapy success in Graves' disease (GD) was analysed. Three questions arised: Did individual estimation of pretherapeutic halflife improve therapeutic success? Did individual dosimetry result in accurate dose calculation? Did antithyroid medication have a measurable influence on therapeutic success under the prevailing conditions? METHODS: 126 consecutive patients were treated with 200 Gy I-131 in our therapy ward for GD and followed-up six to nine months after therapy. Success quote was assessed using a standardized protocol and treatment was classified as successful when the patient was eu- or hypothyroid, or unsuccessful when he or she presented with a suppressed TSH-level or in hyperthyroid condition after antithyroid medication withdrawal. Antithyroid medication, activity I-131, dose, concentration of fT3 and fT4, specific delivered dose and halflife were put into a multiple regression model to assess their influence on therapeutic success. In order to assess possible factors disturbing the therapeutic outcome, relevant parameters were analyzed using Logit transformation. RESULTS: Out of 126 patients 84 were classified as successfully treated and 42 (33.3%) as failures. A significant influence on the outcome only was found for thyroid mass. However, therapeutic success appeared to be more distinctly determined by the specific delivered dose using an estimated halflife of 5.5 days (Odds: 10.0, p < 0.001). Accurate intratherapeutic dosimetry did not play a significant role to enhance therapeutic success. Neither did antithyroid medication during radioiodine therapy exert any significant impact. CONCLUSIONS: Measurement of individual intratherapeutic halflife as opposed to an estimate using a standard halflife did not provide improved results concerning the target dose. Retrospectively, the therapeutic outcome on the basis of a measured halflife as compared to a standard halflife did not significantly improve. In addition, no influence of antithyroid medication on therapy success was found.

[Severe Vitamin D(dihydrotachysterol)-intoxication with temporary anemia and hypercalcemia responsive to bisphosphonates]

Severe Vitamin D(dihydrotachysterol)-intoxication with temporary anemia and hypercalcemia responsive to bisphosphonates. HISTORY AND FINDINGS: A 31-year old female patient presented with pain of her skeletal system. 6 months prior to her presentation, she underwent thyroid surgery for Graves disease. She also suffered from endocrine orbitopathy. Afterwards, she expirienced surgical hypoparathyroidism and received dihydrotachy-sterol (A.T.10 (R)) in a dose of up to 4 mg per day. The physical examination was unremarkable except for the presence of Graves' ophthalmopathy and a swelling at the left ancle. INVESTIGATIONS: Upon admittance, she had severe hypercalcemia (serum calcium: 4.1 mmol/l) with plasma intact PTH levels below the limit of detection, renal failure (serum creatinine: 5.5 mg/dl) and normocytic anemia (initial hemoglobin: 8.3 g/dl, upon rehydration: 6.6 g/dl). TREATMENT AND COURSE: Upon rehydration and induced diuresis, the renal function improved and the serum calcium came down rapidly in the early treatment phase. However, serum calcium remained elevated at around 3.0 mmol/l after 4 weeks. Only after the use of the bisphosphonate pamidronate (15 mg), serum calcium returned into the normal range and remained there. Treatment for hypoparathyroidism had to be reinstituted only 20 weeks after dihydrotachysterol had been discontinued. The anemia had resolved without any treatment at that time. CONCLUSIONS: Treatment with dihydrotachysterol and other long-acting Vitamin D preparations has to be monitored closely because of the risk of severe hypercalcemia, which may be difficult to treat. In our case, dihydrotachysterol was still active until week 20 after the drug was discontinued. Anemia should be considered as a side effect of dihydrotachysterol intoxication and does not warrant elaborate differential diagnosis in this context. A single administration of a bisphosphonate turned out to be of major therapeutic benefit and resulted in a lasting correction of hypercalcemia. Therefore, bisphosphonates should become part of the treatment regimen for vitamin D intoxication.