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Background. Differentiated thyroid carcinoma (DTC) is characterized by an excellent prognosis with a 10-year survival rate > 90%. However, when DTC develops in a metastatic form, it has been shown to significantly impact patient survival and quality of life. Although I-131 has been shown to be an effective therapy in patients with metastatic DTC, whether its efficacy after recombinant human TSH (rhTSH) is comparable to endogenous TSH stimulation by thyroid hormone deprivation (THW) is still debated. Our present study was prompted to compare clinical results obtained in metastatic DTC by I-131 administered after rhTSH and THW stimulation protocols, respectively. Methods. A systematic search on PubMed, Web of Science, and Scopus was performed from January to February 2023. Pooled risk ratios with 95% CI were determined for evaluating the initial response after to I-131 therapy after preparation with rhTSH or THW and the disease progression. To track the accumulation of evidence and reduce type I errors because of small data, a cumulative meta-analysis was performed. A sensitivity analysis was also performed to examine the impact of individual studies on overall prevalence results. Results. Ten studies were included with a total of 1929 patients pre-treated with rhTSH (n = 953) and THW (n = 976), respectively. The cumulative data of our systematic review and meta-analysis showed an increase in the risk ratio over the years without any change in favour of a pre-treatment or the other on the effectiveness of I-131 therapy of metastatic DTC. Conclusions. Our data suggest that pretreatment with rhTSH or THW has no significant impact on the effectiveness of I-131 therapy for metastatic DTC. This implies that concerns about the use of one or the other pretreatment should be deferred to clinical evaluations made considering patient characteristics and reduction in side effects.

ZusammenfassungAus fachfremder Sicht wird der Stellenwert der „konventionellen“ Schilddrüsenszintigrafie zur Klärung diverser thyreologischer Fragestellungen international mittlerweile weit niedriger eingeschätzt, als dies dem hierzulande tätigen Nuklearmediziner bewusst ist. Dieser Aufsatz gibt einen Überblick über häufig geäußerte Kritikpunkte an der Schilddrüsenszintigrafie und möchte einiges hierzu klarstellen sowie in berechtigten Fällen fundierte Gegenargumente liefern. In diesem Rahmen wird ein Überblick über die weiterhin bestehenden Indikationen gegeben, es werden aber auch Aspekte angeschnitten, bei denen Verbesserungsbedarf besteht. Abschließend erfolgt eine Aussicht auf zukünftige Perspektiven und Weiterentwicklungen der funktionellen Charakterisierung von thyreoidalem Gewebe.

Radioiodine-131 treatment has been a well-established therapy for benign thyroid diseases for more than 75 years. However, the physiological reasons of the so-called stunning phenomenon, defined as a reduced radioiodine uptake after previous diagnostic radioiodine administration, are still discussed controversially. In a recent study, a significant dependence of thyroid stunning on the pre-therapeutically administered radiation dose could be demonstrated in patients with goiter and multifocal autonomous nodules. A release of thyroid hormones to the blood due to radiation-induced destruction of thyroid follicles leading to a temporarily reduced cell metabolism was postulated as possible reason for this indication-specific stunning effect. Therefore, the aim of this study was to develop dose-dependent correction factors to account for stunning and thereby improve precision of radioiodine treatment in these indications. A retrospective analysis of 313 patients (135 with goiter and 178 with multifocal autonomous nodules), who underwent radioiodine uptake testing and radioiodine treatment, was performed. The previously determined indication-specific values for stunning of 8.2% per Gray in patients with multifocal autonomous nodules and 21% per Gray in patients with goiter were used to modify the Marinelli equation by the calculation of correction factors for hyperfunctioning radiation-induced stunning (CHRIS). Subsequently, the calculation of the required activity of radioiodine-131 to obtain an intra-therapeutic target dose of 150 Gy was re-evaluated in all patients. Furthermore, a calculation of the hypothetically received target dose by using the CHRIS-calculated values was performed and compared with the received target doses. After integrating the previously obtained results for stunning, CHRIS-modified Marinelli equations could be developed for goiter and multifocal autonomous nodules. For patients with goiter, the mean value of administered doses calculated with CHRIS was 149 Gy and did not differ from the calculation with the conventional Marinelli equation of 152 Gy with statistical significance (p = 0.60). However, the statistical comparison revealed a highly significant improvement (p

Purpose: (i) To examine the criterion taller-than-wide (TTW) for the sonographic assessment of thyroid nodules in areas of iodine deficiency in terms of frequency, anatomical distribution within the thyroid gland and risk of malignancy. (ii) To develop a model for nodule growth in the thyroid gland. Methods: German multicenter study consisting of two parts. In the prospective part, thyroid nodules were sonographically measured in all three dimensions, location within the thyroid gland and contact to a protrusion-like formation (horn) in the dorsal position of thyroid gland was noted. In addition, further sonographic features such as the composition, echogenity, margins and calcifications were investigated. All nodules from the prospective part were assessed for malignancy as part of clinical routine at the decision of the treating physician adhering to institutionally based algorithms. In the retrospective part, only nodules with fine needle aspiration and/or histology were included. The risk of malignancy in TTW nodules was determined by correlating them with cyotological and histological results. Results: Prospective part: out of 441 consecutively evaluated thyroid nodules, 6 were found to be malignant (1.4%, 95% CI 0.6–2.7%). Among the 74 TTW nodules (17%), 1 was malignant (1%, 95% CI 0–4%). TTW nodules were more often located in the dorsal half of the thyroid than non-TTW nodules (factor 2.3, p = 0.01, 95% CI 2.1–2.5) and more often located in close proximity to a horn than non-TTW nodules (factor 3.0, p = 0.01, 95% CI 2.4–3.8). Retrospective part: out of 1315 histologically and/or cytologically confirmed thyroid nodules, 163 TTW nodules were retrieved and retrospectively analyzed. A TTW nodule was 1.7 times more often benign when it was dorsal (95% CI 1.1–2.5) and 2.5 times more often benign when it was associated with a horn (95% CI 1.2–5.3). The overall probability of malignancy for TTW nodules was 38% (95% CI 30–46%) in this highly preselected patient group. Conclusion: TTW nodules are common in iodine deficient areas. They are often located in the dorsal half of the thyroid gland and are frequently associated with a dorsal protrusion-like formation (horn) of the thyroid. Obviously, the shape of benign nodules follows distinct anatomical preconditions within the thyroid gland. The frequency of TTW nodules and their predominant benignity can be explained by a pole concept of goiter growth. The difference between the low malignancy risk of TTW nodules found on a prospective basis and the high risk found retrospectively may be the result of a positive preselection in the latter.

To investigate the interobserver agreement (IA) and the impact of consensus reading using four risk stratification systems for thyroid nodules (TN). Four experienced specialists independently rated US images of 80 TN according to the Kwak-TIRADS, EU-TIRADS, ACR TI-RADS, and ATA Guidelines. The cases were randomly extracted from a prospectively acquired database (n > 1500 TN). The observers were blinded to clinical data. This study was divided into two sessions (S1 and S2) with 40 image sets each. After every session, a consensus reading was carried out (C1, C2). Subsequently, the effect of C1 was tested in S2 with 40 new cases followed by C2. Fleiss’ kappa (κ) was calculated for S1 and S2 to estimate the IA and learning curves. The results of C1 and C2 were used as reference for diagnostic accuracy calculations. IA significantly increased (p

The aim of this study was to investigate in a longitudinal approach whether levothyroxine (LT4) substitution has a different impact on quality of life (QoL) and thyroid related QoL in younger (60 years) with elevated thyroid-stimulating hormone (TSH) concentrations. The study included male and female patients with newly diagnosed, untreated subclinical hypothyroidism defined by TSH>8 mU/l. Patients were recruited throughout Germany from 2013–2016 and evaluated by clinical assessment, blood sampling and questionnaires for health related QoL and thyroid-disease thyroid-related QoL (ThyPRO) at time of diagnosis and six months after initiation of LT4 treatment. We found significantly lower QoL in both young and old patients with subclinical hypothyroidism compared to age-matched healthy individuals. Higher scores on follow-up were found in all patients irrespective of age, indicating better QoL on LT4 therapy. Analysis of the ThyPRO questionnaire showed that old patients experienced less Emotional Susceptibility, Tiredness, and Impaired Day Life on LT4, while young patients reported less Cognitive Complaints, Emotional Susceptibility, and Impaired Day Life compared to baseline assessment. Hypothyroidism with TSH concentrations>8 mU/l is associated with impairment in general and ThyPRO QoL in young and old age. Older patients benefited from LT4 therapy and remarkably show similar degree of improvement as younger patients, albeit with some thematic variation in ThyPRO QoL. Our data confirm current recommendations on initiation of LT4 substitution and suggest that this should not be withheld in elderly with TSH concentration above 8–10 mU/l.

to evaluate the time trend of epidemiology of follicular cell derived thyroid cancer (TC) based on data from a well documented cancer registry.Population based data on TC from Lower Franconia (LF), Germany, within 1981 and 2015 were analysed to estimate the regional epidemiology of TC. The incidence was assessed in 5-year-intervals for gender, histology, and tumor stage.Incidence of TC solely attributable to papillary TC (PTC) doubled mainly in T1- and T2-stages within the evaluation period from 4.5 to 8.7/100.000/y in females and 1.7 to 4.1/100.000/y in males. There was no significant change of follicular TC (FTC), whereas anaplastic TC (ATC) decreased in the same interval. The number of lymph-node metastases and T3-cases increased, while the frequency of T4-stage and distant metastases decreased. Increased incidences of T1- and T2-stages suggest an over-diagnosis. In contrast, increasing number of tumors at T3-stage and with lymph node involvement contradict the over-diagnosis as the only reason for rising incidence. Declining of T4-stages in spite of increasing of T3-stages and N1-cases indicates the value of timely detection and treatment of TC. In accordance, reduced incidence of advanced cancers with M1-stage and ATC cases promote our current management of TC.Timely diagnosis and adequate risk-adopted treatment of thyroid cancer reduce the frequency of high-risk cases with distant metastases and the possible protracted dedifferentiation of TC to anaplastic features. Our analyses support the management algorithm in thyroid cancer according to the recent guidelines of German Nuclear Medicine Society.ZIEL: Evaluierung des Trends der Epidemiologie von Schilddrüsenkrebs (TC) in Unterfranken (UF).Populationsbasierte Daten aus Unterfranken aus den Jahren 1981 bis 2015 wurden analysiert und die Änderung der Inzidenz des TC ermittelt. Die Inzidenz wurde in 5-Jahres-Intervallen in Bezug auf Geschlecht, Histologie, und Tumorstadium berechnet.Die TC-Inzidenz verdoppelte sich im Auswertungszeitraum, bei Frauen von 4,5 auf 8,7/100.000/J und von 1,7 auf 4,1/100.000/J bei Männern, was überwiegend den papillären Schilddrüsenkarzinomen (PTC) in T1- und T2-Stadien zuzuschreiben ist. Es gab keine signifikante Änderung beim follikulären TC (FTC), während die Häufigkeit des anaplastische TC (ATC) abnahm. Die Anzahl der Lymphknotenmetastasen und T3-Fälle stieg, während die Frequenz der T4-Fälle und der Fernmetastasen in diesem Intervall abnahm. Eine erhöhte Inzidenz von Karzinomen in T1- und T2-Stadien ließe sich durch Überdiagnostik erklären. Im Gegensatz dazu sprechen die Zunahme der Inzidenz von Tumoren in T3- und N1-Stadien gegen eine Überdiagnose als einzigen Grund für den Anstieg. Die abnehmende Zahl von Patienten mit T4-Stadium bei gleichzeitigem Anstieg der Fälle im T3- und N1-Stadium sprechen vielmehr für eine rechtzeitige Diagnose von Schilddrüsenkarzinomen. Die abnehmende Inzidenz der weit fortgeschnittenen Fälle mit Fernmetastasen und mit ATC im gleichen Zeitraum bestätigen das bei uns verfolgte Konzept.Die rechtzeitige Diagnose und adäquate risikoadaptierte Behandlung des Schilddrüsenkarzinoms im Frühstadium reduziert die Häufigkeit von Hochrisiko-Fällen mit Fernmetastasen und verhindert die mögliche Entdifferenzierung vom DTC zu anaplastischen Tumoren. Unsere Analysen bestätigen das therapeutische Management von Schilddrüsenkrebs gemäß Leitlinien der Deutschen Gesellschaft für Nuklearmedizin.

Both, ultrasonography but also radionuclide imaging using [99mTc]Pertechnetate or radioactive iodine isotopes are essential tools used during the diagnostic workup of hyperthyroidism with or without structural alterations of the thyroid. Colour duplex sonography and ultrasound elastography may add important information in order to find the cause of the hormone excess. During the last years, also hybrid imaging using SPECT/-(CT) or PET-based methods, such as [124]Iodine-PET/CT or [124]Iodine-PET/ultrasound also have nodularbeen increasingly used and especially play a role in the context of localizing ectopic thyroid tissue or in multinodular goiter. Recently also promising data has been published on the use of [99mTc]MIBI imaging in amiodarone induced hyperthyroidism.

Objective The usefulness of routine calcitonin measurement for early detection of medullary thyroid carcinoma (MTC) in patients with nodular thyroid disease (NTD) has been investigated in various studies. Recently, a Cochrane review has been published on this issue, but a meta-analysis is lacking yet. Therefore, we performed this meta-analysis. Methods We performed an electronic search using PubMed/Medline, Embase and the Cochrane Library. Studies assessing the diagnostic accuracy of routine calcitonin measurement for detecting MTC in patients with NDT were selected. Statistics were performed by using Stata software, risk of bias was assessed using Review Manager version 5.3. Results Seventeen studies, involving 74,407 patients were included in the study. Meta-analysis, using the bivariate random effects model and the hierarchical summary receiver operating characteristic (HSROC) curve revealed the following pooled estimates: sensitivity 0.99 (95% CI, 0.81–1.00), specificity 0.99 (95% CI, 0.97–0.99), positive likelihood ratio (L+) 72.4 (95% CI, 32.3–162.1), and negative likelihood ratio (L−) 0.01 (95% CI, 0.00–0.23). Meta-regression analysis showed that the threshold of basal calcitonin is an independent factor, but in particular performing stimulation test is not an independent factor. Conclusions We showed that routine basal serum calcitonin measurement in the management of patients with thyroid nodules is valuable for the detection of MTC. However, the published cut-off values should be considered and, if applicable, the patients monitored in a wait-and-see strategy by experienced physicians to avoid overtreatment.

Thyroid nodules are a common finding, especially in iodine-deficient regions. Ultrasonographic scoring systems such as the Thyroid Imaging Reporting and Data System (TIRADS) are helpful in differentiating between benign and malignant thyroid nodules by offering a risk stratification model. Depending on the constellation or number of suspicious ultrasound features, a fine-needle biopsy is recommended. However, none of the previous TIRADS publications considered the functional status of the nodules. Hyperfunctioning thyroid nodules (HTNs) were presumed to exclude malignancy with a very high negative predictive value. Particularly in regions where the iodine supply is low, most HTNs are seen in patients with normal thyroid-stimulating hormone levels. Therefore, thyroid scintigraphy is essential for the detection of HTNs. We investigated whether TIRADS identifies HTNs as nonsuspicious. Methods: We evaluated 615 HTNs (23.2 ± 10.0 mm in maximum diameter in 582 patients ([442 women, 57.7 ± 13.2 y old, and 140 men, 60.1 ± 12.7 y old) detected by 99mTc-pertechnetate or 123I scintigraphy. Before evaluating the scintigraphic appearance, all nodules were analyzed prospectively with sonography, using the TIRADS model referenced in Kwak et al., wherein fine-needle biopsy is recommended for TIRADS 4A or higher. We also investigated 2 subgroups, 42 nodules with available histology and 117 patients with subclinical or overt hyperthyroidism. Results: Whereas 15.9% of the nodules were classified as TIRADS 3 or lower and less than 0.1% as TIRADS 5, most of the nodules were classified as TIRADS 4A (29.3%), 4B (29.3%), or 4C (24.9%). Altogether, more than 80% of the autonomous thyroid nodules were classified as TIRADS 4A or higher, a grade that would result in a recommendation of fine-needle biopsy. Focusing on those 117 HTNs that were already associated with hyperthyroid laboratory values, the rates were similar: 81.2% were categorized as TIRADS 4A or higher (4A, 33.3%; 4B, 29.9%; 4C,17.1%; 5, 0.9%). In the subgroup of patients who underwent thyroid surgery, all nodules were benign, confirming the known negative predictive value of HTNs with regard to malignancy exclusion. Conclusion: Integration of thyroid scintigraphy into the TIRADS model is essential to prevent unnecessary fine-needle biopsy and thyroid surgery.

Calcitonin (hCt) ist ein vergleichsweise anspruchsvoller Parameter – sowohl hinsichtlich der Probenbehandlung als auch der Interpretation der Laborergebnisse sowie der hieraus zu ziehenden Konsequenzen. Hinsichtlich der Referenzbereiche sollten geschlechtsspezifische Unterschiede berucksichtigt werden. Die Aussagekraft des Kalzium-Stimulationstests zur Abklarung nur masig erhohter hCt-Basalwerte ist derzeit umstritten; hier besteht noch weiterer Bedarf zur Optimierung bzw. Standardisierung der Durchfuhrung und Interpretation der Ergebnisse. Sofern erwogen wird, hCt im Rahmen eines Screenings bei nodularem Schilddrusenbefund oder als Tumormarker in der Verlaufskontrolle behandelter medullarer Schilddrusenkarzinom-Patienten zu bestimmen, mussen einige Rahmenbedingungen sichergestellt sein. Hierzu gehoren insbesondere: optimale praanalytische und stabile laborchemische Bedingungen, Etablierung kontrollierter geschlechtsspezifischer Interventionsschwellenwerte, ein Recall-System fur Patienten mit zunachst kontrollbedurftigen Werten, die Verfugbarkeit von validierten Stimulationstests im Falle fraglich pathologischer basaler hCt-Werte, Kenntnis moglicher Einflussparameter auf die Messwerte, eigene Expertise hinsichtlich der Besonderheiten des medullaren Schilddrusenkarzinoms (MTC) und die enge interdisziplinare Kooperation zwischen Nuklearmedizin, Endokrinologie, Chirurgie und Pathologie.

SummaryAim: Several studies described the ultrasound based real-time elastography (USE) having a high sensitivity, specificity and negative predictive value in the diagnosis of suspicious thyroid nodules. Recently published studies called these results into question. Until now the usefulness of USE in the diagnosis of scintigraphically hyperfunctional thyroid nodules is not examined. Patients, methods: This study included 135 hyperfunctional thyroid nodules of 102 consecutive patients. The following attributes of the nodules were analyzed: stiffness with the USE using scores of Rago or Asteria and ultrasound criteria using TIRADS. Results: 94 of the examined thyroid nodules (70%) were rated as hard (suspicious for malignancy) and 41 nodules (30%) as soft (not suspicious) with a specificity of 30%. The scoring systems of Rago and Asteria showed no sigificant difference. Applying the TIRADS criteria 44 nodules (33%) have a higher risk for malignancy (33 nodules TIRADS 4a, 11 nodules TIRADS 4b). Combining USE and TIRADS 32 nodules (24%) are categorized as suspicious (intersection of hard nodules that are categorized as TIRADS 4a or 4b). Conclusion: Ultrasound based real-time elastography cannot identify scintigraphically hyperfunctional thyroid nodules as benign nodules reliably. Its accuracy in the assessment of at least “hot” thyroid nodules is to be questioned.

Background: An association between smoking and the risk of goitre is reported in some, but not all studies. We investigated the association between smoking, goitre and iodine intake, with respect to different risk factors in 483 healthy men in Germany. Methods: A total of 483 healthy male employees of 4 institutions in Essen in Western part of Germany, aged between 17 and 68 years (43.1 ± 9.6 y) were examined by ultrasound of the neck to determine the thyroid volume between April 2001 and April 2002. Information on age, BMI, smoking, daily use of iodized salt, and familial history of thyroid disorders were assessed by standardized questionnaires. Logistic regression analysis was performed to adjust for smoking, age, iodine status and familial history of goitre. Results: The overall prevalence of goitre was 25.7%. Median thyroid volume among smokers, (23.4 ± 10.1 ml), was higher (p

Item does not contain fulltext BACKGROUND: Tumor marker doubling time (DT) has been proposed as a prognostic marker for various types of cancer. The present study analyzed the DT of the thyroid-specific tumor marker thyroglobulin (Tg), focusing on patients with progressive differentiated thyroid cancer (DTC). METHODS: A total of 144 Tg courses of 99 patients with progressive or recurrent DTC were included (median observation period 19 months, 3-11 Tg measurements per course) in this retrospective study. The distribution of Tg-DT was determined for both a highly sensitive assay (functional working range 0.03-3 ng/mL) and a routine assay. Tg-DT and other prognostic markers were used to perform uni- and multivariate statistical analyses for survival predictors. RESULTS: The median Tg-DT was 212 days (95% percentile: 49-961 days). No significant differences were observed between DT derived from Tg values in the very low range using a highly sensitive assay and DT calculated from Tg values measured by a conventional Tg assay. Multivariate analysis yielded no simple correlation between Tg-DT and survival rate, but the mortality risk of patients with a Tg-DT 14 months. Highly significant differences on survival rates were only observed in patients with a high tumor load (Tg >100 ng/mL). CONCLUSIONS: Tg-DT alone is not an independent survival predictor in all patients with progressive DTC; however, analyzing only patients with a high tumor load, we found highly significant differences in survival rates.

Background: To evaluate the predictive factors of goitre prevalence in females. Methods: In a questionnaire-based survey, data from 370 female employees aged between from 4 institutions in western part of Germany was collected between April 2001 and April 2002 and the association between parity and simple goitre was examined with respect to age, daily use of iodized salt, contraceptives, the history of goitre in the first degree relatives and smoking. Ultrasound of the neck was performed in all cases to determine the thyroid volume. Logistic regression analyses were performed to adjust for age, iodine status, parity, contraceptives, familial history of goitre and smoking. Results: The overall prevalence of goitre was (80/370) 21.6%. Median thyroid volume Goitre was present in 44 out of 140 parous (31.4%) vs. 34/220 (15.5%) in nulliparous (odds ratio: 2.5; p

Summary Context In patients with differentiated thyroid carcinoma (DTC) who, after thyroidectomy, are to receive radioiodine therapy or diagnostics, a strong TSH stimulus is necessary. Traditionally, this is induced by thyroid hormone withdrawal (THW) over a period of 4–5 weeks; alternatively thyroid hormone replacement therapy is continued and recombinant human thyrotropin (rhTSH) is administered. During the hypothyroid state due to THW, patients often report mood disturbances and physical complaints but also an impairment of performance during attention demanding tasks. Objective Based on physiological, self-report and performance test data collected from various studies, we proposed the hypothesis that thyroidectomized DTC patients perform significantly worse in cognitive-motor functions that are relevant for driving when in the THW-induced hypothyroid state compared to when thyroid hormone replacement therapy is continued and rhTSH is administered. Methods We compared 41 DTC patients (age 42.3 (9.4) years; 80.5% female) after 4 weeks THW with 41 DTC patients after the application of rhTSH, pairwise matched according to age, gender and educational level, with respect to performance in 4 core tests of the Act-React-Testsystem ART-90, a validated test battery for examining fitness to drive. Results Contrary to our expectations, no statistically relevant impairment of performance could be confirmed in the THW group in comparison to the rhTSH group for any variable (at adjusted α). At most there is a tendency in the THW group for slowed reaction times in simple-choice reaction tasks; the (standardized) difference to the rhTSH group is however small (d′ = 0.31). Furthermore, large effects due to THW, as they are suggested by several studies, could be excluded.

Purpose Advanced tumour stage and initial metastases are associated with reduced general and tumour-free survival in patients with differentiated thyroid carcinoma. Optimal initial therapy is mandatory for a positive patient outcome, but can only be performed if all non-iodine-avid tumour lesions are known before planning treatment. We analysed the benefit of 18F-FDG PET/CT at initial diagnosis in patients with high-risk differentiated thyroid carcinoma and determined whether the 18F-FDG PET/CT results led to a deviation from the standard procedure, which consists of two consecutive radioiodine treatments with thyroid hormone suppression in between and no additional imaging, with individual patient management.

Die Radioiodtherapie des differenzierten Schilddrusenkarzinoms hat eine 70-jahrige Tradition. Sie wird sehr gut toleriert, ist nebenwirkungsarm und tragt einen substanziellen Anteil zur guten Prognose der Erkrankung bei. An den Grundprinzipien der Therapie hat sich nichts geandert. Voraussetzung fur den Erfolg ist die gute Aufnahme des Iods in die Schilddrusenkarzinomzelle und die moglichst lange Retention. In den letzten Jahren sind verschiedene Innovationen zu verzeichnen. Die fur die Iodaufnahme fur erforderlich gehaltene TSH-Stimulation ist seit einigen Jahren auch mittels rhTSH-Injektionen moglich, wodurch die durch den Schilddrusenhormonentzug bedingten hypothyreoten Beschwerden vermieden werden konnen. Eine zuverlassige und vorhersagbar positive (im Sinne einer hoheren Lasionsstrahlendosis) Beeinflussung der Iodkinetik ist derzeit jedoch weiterhin nicht bekannt. Die Gabe von Li + konnte ebenso hilfreich sein wie andere Modalitaten zur Beeinflussung der Iodkinetik, die von der Behandlung gutartiger Schilddrusenerkrankungen her bekannt sind. Die Identifizierung von Patienten, bei denen eine kurative Radioiodtherapie nicht zu erwarten ist, wird durch die Dosimetrie mit 124 I – PET/CT moglich und daruber hinaus mittels der pratherapeutischen Dosimetrie auch die individuelle Festsetzung der 131 I-Therapieaktivitat. Durch die Einfuhrung der SPECT/CT steht eine Gammakamera-basierte Schnittbilddiagnostik mit anatomischer Korrelation auch mit dem Therapienuklid 131 I zur Verfugung, wodurch die Aussagekraft der Post-Therapie-Szintigrafie gesteigert wird.

BACKGROUND Calcitonin (CT) is a sensitive marker for evaluation of medullary thyroid cancer (MTC). However, CT measurement can vary with assay- and nonassay-dependent factors, and procalcitonin (PCT) measurement has been proposed for evaluating questionable increases in CT. METHODS We tested 2 fully automated CT assays (Immulite [IL] and Liaison [LIA]) and 1 nonautomated CT assay (IRMA, Medipan) and compared these results with PCT (Brahms Kryptor). We evaluated preanalytical conditions and PCT cross-reactivity in sera of 437 patients with clinical conditions associated with hypercalcitoninemia. Additionally, we determined the true “nil” CT concentration in 60 thyroidectomized patients and defined CT cutoff concentrations for pentagastrin stimulation testing in 13 chronic kidney disease (CKD) patients and 10 MTC patients. RESULTS Markedly decreased CT concentrations were found after storage of sera for >2 h at room temperature and >6 h at 4 °C. Cutoff concentrations for basal and stimulated CT were disease and assay dependent. Proton pump inhibitor therapy was the most frequent reason for increased CT. PCT concentrations were higher in patients with MTC than in patients with CKD without infections (P < 0.001). Whereas IL and LIA demonstrated comparable analytical quality, the IRMA gave increased CT concentrations in nil sera and showed cross-reactivity with PCT in patients with concomitant bacterial infection. CONCLUSIONS IL, LIA, and IRMA detected increased CT concentrations in non-MTC patients and discriminated MTC from CKD patients in pentagastrin tests. PCT assessment may be helpful in the diagnostic work-up of increased CT concentrations in questionable clinical circumstances.

SummaryObjective: Optimization of a specially developed automatic microaspirator for fine-needle aspiration of suspicious thyroid nodules. Patients, method: In a preliminary test biopsy effectiveness was evaluated in 20 native resected thyroid glands in vitro with both a Cameco® gun and a specially designed microaspirator respectively. In addition in both techniques two different needles (21-G and 27-G) were used to evaluate the influence of these two cannula. Subsequently, 103 thyroid nodules were biopsied in vivo and compared the results with a preliminary series of the same physician. In the workup and evaluation of the cytology the ThinPrep® technology was used. Results: In vitro the automatic microaspirator was superior to Cameco gun in both when using the 21-Gauge and the 27-Gauge needle. In terms of needle sizes a statistically significant difference at the 95% confidence level was evident for both comparisons in favor of 21-gauge needle. In vivo, 91% of punctures with the microaspirator were usable, while in the pre-series only 84% were usable (p > 0.05). Conclusion: The automatic microaspirator is superior to the manual aspiration. Moreover, under sonographic control it is more convenient, to biopsy even very small nodules and lesiosn (down to 4 mm in diameter)

Ziel: In den vergangenen Jahren wurden von verschiedenen Fachgesellschaften Leitlinien zur diagnostischen Abklarung von Schilddrusenknoten publiziert, in denen die Indikation zur Szintigraphie beschrankt wird auf Patienten mit subnormalen TSH-Werten. Es wird kontrovers gesehen, ob diese Empfehlungen auf Deutschland ubertragen werden sollten, u. a. wegen der hierzulande geringeren Iodversorgung und des dadurch bedingten hoheren Anteils fokaler Autonomien, die nicht mit messbarer Dysfunktion einhergehen. Da hierzu kaum belastbare Daten publiziert sind, wollten wir multizentrisch das Spektrum szintigraphisch „heiser“ und „warmer“ Knoten unter aktuellen epidemiologischen Bedingungen analysieren. Patienten, Methoden: In 10 nuklearmedizinischen Praxen in unterschiedlichen Regionen Deutschlands werteten wir die diagnostischen Daten von 514 Patienten aus, bei denen sich mittels 99mTc-Pertechnetatszintigraphie eindeutig mehranreichernde Knoten (fokale Mehranreicherungen im Vergleich zum perinodularen Gewebe mit sonographischem Knotenkorrelat ≥1 cm) nachweisen liesen. Um den Selektionsbias zu minimieren, wurden die Erhebungen nicht in Kliniken durchgefuhrt. Zu den erfassten Parametern gehorten die Schilddrusenhormonwerte, der globale 99mTc-Uptake (TcTU), die Grose der einzelnen Knoten und das autonome Gesamtknotenvolumen (Vaut). Ergebnisse: Lediglich bei 20% der Patienten mit „heisen“ Knoten lagen die TSH-Werte im subnormalen Bereich (

Thyroglobulin and calcitonin are established humoral tumor markers for therapy monitoring and follow up of thyroid cancer of follicular origin or medullary thyroid cancer, respectively. In comparison to many other tumor markers these analytes offer a high diagnostic specificity, which increases with the radicalness of thyroid ablation. Over the last years, assays with rising functional sensitivity became commercially available, being however a challenge in respect to laboratory performance, quality assurance and medical judgement in the „ultrasensitive” range of detectable concentrations. Anyway, hTg and hCT must be considered to be ambitious laboratory parameters. The results considerably depend on various in vivo and in vitro influences, and even under constant conditions, different assays may not necessarily produce identical results. hCt assays that measure the monomer (mature) calcitonin form have the advantage of an enhancement of the diagnostic specificity. Apart from follow up investigations in treated MTC patients, a couple of medical societies assume hCt measurement to be justified in the presence of a thyroid nodule. In contrast, guidelines do not recommend hTg measurement as a routine procedure for the assessment of the malignancy of thyroid nodules. However, hTg measurement may have an indication in differential diagnosis of connatal hypothyroidism, in assumed thyrotoxicosis factitia and as a marker of destructive thyroidal disease like subacute or amiodarone-induced thyroiditis.

Radioiodine therapy of benign thyroid diseases (focal = [toxic adenoma], multifocal, disseminated autonomy, Grave's disease or clinical relevant goitre) needs to be and can be performed individually for each patient. Most frequently a radioiodine test is performed applying a small activity of iodine-131 ( 131 I). The paper discusses some protocols for pre- or posttherapeutic dosimetry and discusses their advantages and disadvantages. All are based on the volumetry of the target tissue as well as the radioiodine kinetics in the target volume what may be represented by maximum uptake and half life of iodine retention in the thyroid. Possible disturbances and measuring uncertainties of these parameters are presented and discussed. In spite of the discussed uncertainties in dosimetry, due to its high therapeutic width radioiodine therapy is a very successful procedure to cure hyperthyroidism or to reduce goitre volume with only little side effects.

AIM: The influence of various geometric factors on I uptake measurements for solitary thyroid nodule was systematically investigated to derive an approach, based on routinely performed ultrasound examinations, to correct for the effect of geometric variations. METHODS: The influence of size, shape, and position of a thyroid nodule, neck-to-detector distance and neck curvature on the uptake value was analyzed with a three-dimensional model. Uptake measurements using a tissue-equivalent neck phantom were carried out to verify the calculated correction factors and also to check the influence of scatter. Sonograms of 92 patients with solitary nodules were analyzed to correct for geometric variations. RESULTS: The correction factors were independent of the size and shape of the nodule, and the activity distribution of the solitary nodules can be approximated by a point source. The correction factors were mainly determined by the nodular depth and by the accuracy of the neck-to-detector distance and were affected to a lesser extent by the lateral position of the nodule as well as the curvature of the neck. The effect of scatter can be neglected if the energy window largely excludes Compton scatter, as is the case in the I uptake measurement. The ultrasound-derived correction factors ranged from 0.85 to 1.25. CONCLUSION: The proposed approach is capable of correcting for the geometric variation for a solitary nodule and can be easily applied in routine clinics. The accuracy of absorbed dose in radioiodine therapy can be improved in particular for nodules located well beneath the neck surface.

SummaryAims: Objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. Patients, methods: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48h post i.v. injection of 175–200 MBq 111In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in >50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR®-Depot 30mg i.m. every four weeks). Results: In 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In two patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a twomonth interval showed progressive disease in both patients. Conclusions: We conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option.

Rationale and Objectives In recent years, picture archiving and communication systems and electronic transfer of radiologic images using the digital imaging and communications in medicine file standard has become more widely employed in diagnostic radiology. It seems to be likely that nuclear medicine will be integrated within such systems. On the other hand, many departments possess older nuclear medicine equipment without digital output facilities. There is an increasing tendency to display and archive evaluated images (“save-screens,” printouts) on nondedicated, inexpensive systems using file formats capable of data compression. This was the reason for examining the value of the JPEG format in this pilot study. Materials and Methods Fifty scanned planar bitmap images of the most frequent scintigraphic examinations (thyroid, bone, myocardium, lungs, and kidneys) were compared with JPEG format at different data compressions by two blinded observers. The visualization of details (eg, pathologic findings) is described for all these images as the visual appearance of the images and the storage capacity required. Results Relevant loss of clinical information did not occur up to compression factors of 0.75. A major decrease of subjective image quality was seen at compression factors >0.90. Compared with bitmap files, the use of these factors reduced the storage capacity required by 98% at a (JPEG-related) compression factor of 0.50, and 99% at a compression factor of 0.90. Compared with the GIF format, a reduction by 4.0–5.7 could be achieved. Conclusions Use of the JPEG format can therefore be recommended to save costs of image transfer or archiving of standard planar scans for nuclear medical evaluation.

Zusammenfassung Hintergrund: Depressivitat und Angstlichkeit zahlen bei Patienten mit Schilddrusenkarzinom (DTC) zu den haufigsten Befindlichkeitssymptomen mit einem wichtigen Einfluss auf die Lebensqualitat. In der vorliegenden Studie wurde das Ziel verfolgt, protektive Faktoren fur Depression und Angst bei DTC-Patienten zu identifizieren. Methodik: In einer konsekutiven Querschnittstudie wurden 230 DTC-Patienten mit der Hospital Anxiety and Depression Scale (HADS-D), der Sense of Coherence Skala (SOC) und dem Fragebogen zu Sozialer Unterstutzung (F-SOZU) untersucht. Ergebnisse: Eine hoch signifikante Korrelation zeigte sich zwischen Depression und Angstlichkeit (r = .633, p = 0,001). Soziale Unterstutzung und Sense of Coherence hingegen korrelierten sehr signifikant negativ sowohl mit Depression als auch mit Angstlichkeit (beide p 0,001). Geringer, dennoch signifikant, fiel die Korrelation zwischen Alter und Angstlichkeit aus (r = -.19; p 0,005). Der TSH-Spiegel als Mas fur die Auspragung der Hypothyreo...

Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both (124)I-NaI and (18)F-FDG along with high-resolution cervical ultrasound.Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by (18)F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in (124)I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in (18)F-FDG PET/CT. Survival analyses were performed using Kaplan-Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS).Incomplete metastatic lymph node resection captured by (124)I-NaI PET/CT (n = 33) was an independent risk factor for recurrence (61 % vs 25 %, p = 0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7-9.2], p = 0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69 months, p = 0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3), only large tumor size (pT4) had a significant impact on PFS (HR 2.9 [95 %-CI, 1.3-6.4], p = 0.007).Incomplete initial surgical clearance of lymph node metastases even after successful radioiodine therapy may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT) imaging with (124)I-Na and (18)F provides a prognostic tool for these patients and may considerably complement the current risk stratification systems.

To estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy.Fifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1-21 GBq (131)I using single activities of 1-6 GBq. The patients were stratified according to the cumulative activities into low-activity (1-2 GBq), middle-activity (3-7 GBq), and high-activity groups (9-21 GBq). The time-activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models.The median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy.GBq (range, 0.1-0.3 Gy.GBq(-1)) and 0.48 Gy.GBq(-1) (range, 0.2-1.2 Gy.GBq(-1)), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups.The iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered (131)I activity was not significantly decreased during the course of therapy. Comparing the well-known dose-effect relationships in external radiation therapy, the absorbed dose per administered (131)I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of (131)I in human salivary glands.

Objectives: We examined the relationships among physical complaints, health-related quality of life (HRQL), anxiety and depression in differentiated thyroid cancer (DTC) patients under short-term hypothyroidism. Methods: We conducted a cross-sectional study in 136 patients hypothyroid on thyroid hormone withdrawal (THW) hospitalized for radioiodine administration. Patients were assessed using Short Form SF-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Beck Depression Inventory (BDI), and physical complaints. Results: Compared to the German general population, hypothyroid patients had significantly impaired HRQL. Surprisingly, the prevalence of anxiety (62.5%), but not depression (17.9%) was much higher in hypothyroid DTC patients than in the general population. In multivariate analysis, depression and age were independently associated with the physical health score (R 2 = 0.21), but only psychological variables (depression, mood disturbance, and anxiety) were associated with the mental health score (R 2 = 0.43), on the SF-36 HRQL instrument. Conclusions: HRQL is severely impaired in DTC patients under short-term hypothyroidism. As potential predictors of generic HRQL impairment, depression, anxiety, and mood disturbance could be used to preselect the patients most needing psychiatric care. The high frequency of anxiety should be considered in the aftercare of thyroid cancer patients.

A C825T polymorphism has been demonstrated in the GNB3 gene that encodes the Gβ3 subunit of heterotrimeric G proteins. Due to enhanced G protein activation, the GNB3 825T allele is associated with an increased signal transduction activity. To elucidate a possible role in the development and course of thyroid tumours of follicular cell origin, C825T polymorphism genotypes and allele frequencies were investigated in a series of adenomas and differentiated carcinomas. Genotypes and the allele frequency of the Gβ3 polymorphism were investigated in samples from 361 patients (all white Caucasians) with differentiated thyroid tumours of follicular cell origin [80 adenomas and 95 follicular (FTCs) and 186 papillary carcinomas (PTCs)]. The results were compared with those of 1859 healthy controls. Both the genotype distribution (p = 0.029) and the allele frequency (p = 0.028) of the adenoma group were statistically significantly different from those of the control group. Thyroid adenomas also differed for both parameters significantly from FTCs (p = 0.042 and 0.033, respectively) and PTCs (0.0018 and 0.0081, respectively), whereas no statistical difference was noted between the FTC and PTC groups. Although the biological significance of these observations remains obscure, the results are suggestive of a putative role for the GNB3 polymorphism in thyroid tumour development and/or progression. Further research has to elucidate if, and to what extent, this common germ-line variation influences the TSH-triggered signalling pathways responsible for thyroid function and proliferation. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Objective and design: Cross-sectional studies have reported an increased prevalence of circulating thyroglobulin autoantibodies (TgAbs) in patients with differentiated thyroid carcinoma (DTC). With the advent of more sensitive assays, a longitudinal study monitoring the development of TgAb levels after ablative therapy was warranted. Methods: One hundred and twelve consecutive patients with follicular cell-derived thyroid cancer were followed for 3 years. All patients had been thyroidectomized and received, on average, two radioiodine therapies. Residual tissue was quantified scintigraphically by 131I 24-h uptake. TgAb and thyroglobulin (Tg) serum levels were determined with a sensitive direct radioligand assay and an IRMA respectively. Results: The prevalence of TgAbs at the initial examination was 29% (median 130 U/ml). During follow-up, TgAb levels rose transiently in one-tenth of the patients, but the prevalence of demonstrable TgAbs decreased to 50 U/ml respectively. While the Tg recovery test was valid for all patients, an in vitro dilution assay with TgAb serum reduced Tg values by up to 32%. Conclusions: The development and course of TgAbs in DTC patients cannot be predicted by initial or residual tumour volume, TgAb or Tg levels. The presence of TgAbs, even in low concentrations, may cause Tg underestimation despite valid recovery tests in DTC patients.

Die Punktionszytologie/Feinnadelaspiration (FNA) ist derzeit die verlasslichste diagnostische Methode zur praoperativen Evaluation von Knoten der Schilddruse. Sie ist kosteneffektiv und bietet in der Metaanalyse eine Sensitivitat von 83% und eine Spezifitat von 92%. Die FNA der Schilddruse ist in 70% der Untersuchungen diagnostisch, in 20% unklar oder verdachtig und in 10% der Falle diagnostisch nicht verwertbar. Die Rate falsch-negativer Befunde betragt weniger als 5%, die falsch-positiver Befunde unter 3%. Die Diagnose eines papillaren, medullaren und anaplastischen Karzinoms stellt im Regelfall kein Problem dar; insbesondere in zellarmen Punktaten oder bei gleichzeitig bestehender Entzundung kann aber auch bei diesen Tumoren die definitive Diagnose nicht immer moglich sein. Es muss mit Nachdruck darauf hingewiesen werden, dass die zytologische Unterscheidung eines (minimal-invasiven) follikularen Karzinoms von Adenomen nicht moglich ist. Die FNA der Schilddruse (und ggf. deren Wiederholung) ist als unabdingbare Standarddiagnostik vor der Operation von kalten Knoten zu fordern.

Schilddrusenkarzinome machen etwa 1% aller menschlichen Malignome aus und stellen somit einen eher seltenen Tumortyp dar. Sowohl die Abgrenzung der Karzinome von gutartigen Lasionen (Hyperplasien, Adenome) als auch die fur die weitere Therapie notwendige exakte Klassifizierung der Schilddrusenkarzinome stellen in der taglichen Routinepathologie mitunter eine diagnostische Herausforderung dar. Schilddrusenkarzinome mit Follikelzellursprung werden nunmehr auch in der kurzlich erschienenen WHO-Klassifikation der Schilddrusentumoren aufgrund ihres biologischen Verhaltens in papillare, follikulare, gering differenzierte und anaplastische Karzinome unterteilt. Wahrend die differenzierten Karzinome (papillare und follikulare Karzinome) ganz uberwiegend eine hervorragende Prognose aufweisen, zeigt das gering differenzierte Karzinom eine deutlich schlechtere und das anaplastische Karzinom in der Regel eine infauste Prognose. Das von den C-Zellen ausgehende medullare Karzinom tritt in einer sporadischen und familiaren Form auf. Das familiare medullare Karzinom wird autosomal-dominant vererbt und kann heute in fast allen Fallen durch entsprechende Mutationen des RET-Protoonkogens nachgewiesen werden.

Objective: Ultrasonography is an established diagnostic modality in the follow-up of thyroid cancer. Color flow Doppler has been proposed by some authors as an additional tool for differentiating benign from malignant cervical lesions in various types of head and neck cancer. Over the last few years, a new generation of high-resolution ultrasound platforms with the ‘power-mode’ feature has become available, that also enables the imaging of small vessel blood flow. The objective of our study was to find ways of optimizing the differentiation of benign and malignant cervical tumors in thyroid cancer follow-up by means of sonography. Methods: Hundred and twelve cervical lesions in 90 patients with thyroid cancer were evaluated by high-end ultrasonography (Sonoline™ Elegra, Siemens) using a small-part transducer (7.5 L 40, Siemens). B-mode sonography was performed at a frequency of 8 MHz. The Solbiati index (SI= ratio of largest to smallest diameter), configuration, echogenicity, intranodular structures, and margins were assessed. Perinodular and intranodular blood flow was evaluated by color flow Doppler (PRF 1250 Hz for conventional color flow Doppler, 868 Hz for power-mode Doppler). Possible malignancy was validated by histology, cytology, scintigraphy, and follow-up. Thirty five lesions were benign (diameter 0.4–3.0 cm) and 77 were malignant (0.4–5.4 cm). The patients were randomized into a test group and a learning group to determine the diagnostic value of various ultrasound criteria by means of statistical analysis. In the learning group, decision rules based on the dichotomized criteria were developed using a logistic regression model. Sensitivity and specificity of these decision rules were then evaluated in the test group. Results: The presence of an echocomplex pattern or irregular hyperechoic small intranodular structures (criterion A) and the presence of an irregular diffuse intranodular blood flow (criterion B) are the best indicators of malignancy, whereas an SI≫2 is highly indicative of benign changes. Color flow Doppler is a useful addition to B-mode scanning for distinguishing benign and malignant neoplasms in the follow-up of thyroid cancer. Power-mode Doppler sonography significantly improves imaging of perinodular and intranodular blood flow when compared with conventional color flow Doppler. Conclusion: We propose the following decision rules based on a combination of the criteria above: (A) and (B) fulfilled: malignant, if SI≤4; (B) but not (A) fulfilled: malignant, if SI≤3; (A) but not (B) fulfilled: malignant, if SI≤2; neither (A) nor (B) fulfilled: malignant, if SI≈1 (sensitivity: 90%; specificity: 82%; accuracy 88%).

Early diagnosis of medullary thyroid carcinoma (MTC) can improve long-term prognosis. MTC can be detected at an early stage by calcitonin screening in all patients with thyroid nodules. This approach, however, is controversial due to high costs and a limited specificity of calcitonin. It was the aim of the present study to investigate whether ultrasonography may contribute to the diagnosis of MTC in patients with thyroid nodules. The study included 19 patients with newly diagnosed MTC. Ten patients had sporadic MTC, 7 had multiple endocrine neoplasia (MEN) type 2A, and 2 patients had MEN 2B. In all subjects conventional ultrasound, and in 14 patients color Doppler sonography were performed before primary surgery. For comparison, ultrasound appearance of 139 benign thyroid nodules was evaluated. In conventional ultrasound, MTC in 17/19 (89%) patients were hypoechoic, contained intranodular calcifications, and had no "halo sign". The combination of these criteria were found in only 8/139 (6%) of benign thyroid nodules. Intranodular blood flow was found in 11/14 patients with MTC (79%), perinodular blood flow in 7/14 MTC (50%). In conclusion, conventional ultrasound reveals a combination of hypoechogenicity, intranodular calcifications, and absence of "halo sign" in the vast majority of MTC. Since this sonographic pattern only rarely occurs in benign thyroid nodules, the results indicate that thyroid ultrasound can contribute to the diagnosis of MTC. In addition, the findings may have implications for calcitonin screening in nodular thyroid disease.

Objective, design and methods: Although TRH testing has been eliminated in the diagnosis of most benign thyroid diseases, it is still controversial whether or not it can be replaced by ultrasensitive determination of basal TSH for monitoring optimal TSH suppression in thyroid cancer patients. We compared basal and TRH-stimulated TSH values measured by a 2 nd generation assay (lower detection limit 0.1 mU/I) and by a 3 rd generation assay (lower detection limit 0.005 mU/l) in 209 thyroidectomized thyroid cancer patients under suppressive levothyroxine treatment. Results: In the 2 nd generation assay all patients had basal TSH values

The thyrotropin receptor-cAMP pathway is central in growth regulation of thyroid cells and thyroid tumorigenesis, and it regulates expression of thyroid specific genes. Recently, 2 new protein kinase A-independent cAMP effectors named EPAC1 and 2 were described that activate additional intracellular pathways. The aim of our study was to investigate the role of EPAC proteins in growth regulation of thyroid cells and thyroid carcinomas. EPAC1 expression was investigated immunohistochemically in tissues of various thyroid tumors. Utilizing MTT assay, the effect of EPAC stimulation on proliferation in thyroid carcinoma cells and in non-transformed rat FRTL5 cells was investigated. The activation of intracellular signaling pathways was examined by RAP pull-down assay and Western blots. EPAC1 expression was strong in non-oxyphilic follicular thyroid adenomas and carcinomas and in follicular papillary thyroid carcinomas. It was moderate in oxyphilic follicular tumors and classical and tall cell papillary carcinomas. In contrast, EPAC1 expression was low in poorly differentiated carcinomas and very low in anaplastic carcinomas. Thyroid carcinoma cell lines showed no or very weak EPAC1 expression and exhibited no growth-promoting effect after EPAC stimulation. Non-transformed rat FRTL5 cells were growth-stimulated by an EPAC-specific cAMP-analogue and showed EPAC-dependent activation of RAP, ERK, and p70S6 kinase. EPAC1 expression and cellular response to EPAC activation in rat FRTL5 cells reflect cellular responses to cAMP and TSH stimulation in non-transformed thyroid cells. In undifferentiated thyroid carcinomas, loss of EPAC1 expression may be in accordance with the loss of thyroid-specific functions and the loss of responsiveness of the TSHR-cAMP pathway.

Routine follow-up of patients with well-differentiated thyroid cancer (WDTC) includes whole-body 131I scintigraphy and serum thyroglobulin determination. Limitations in detecting locoregional recurrence or distant metastases occur when progressive dedifferentiation of thyroid carcinoma cells leads to a loss of iodine-concentrating capacity. In the course of the disease, false-negative radioactive iodine scans are seen in up to 20% of patients with original WDTC. In contrast to the otherwise encouraging overall prognosis of WDTC, this subpopulation of patients may have a poor outcome because of delayed detection of tumor relapse and consecutive surgical treatment. In addition, metastatic thyroid lesions that fail to concentrate radioactive iodine exhibit more aggressive biologic behavior. Several conventional imaging techniques, such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), have been used to localize tumor deposits in the presence of negative 131I scans and clinical suspicion based on an increased serum thyroglobulin concentration in the absence of thyroglobulin antibodies or disturbance of the thyroglobulin recovery test. However, all these anatomic imaging tools can produce varied and inconsistent results, especially in patients undergoing repeated surgical procedures. In the neck, where metastases most frequently occur, the sensitivity and specificity of ultrasound are strongly dependent on subjective factors. 1 For CT and MRI, the overall error rate of assessment of cervical lymph node metastases is 7.5%. 2 The results of nonspecific scintigraphic examinations with 201Tl and 99mTc-sestamibi are unsatisfactory, with an average reported sensitivity of 60%. Recently, numerous reports have shown high utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the detection and staging of different malignant tumors: soft tissue sarcomas;3 cutaneous melanoma;4 pancreatic, 5 breast, 6 colorectal, 7 esophageal, 8 head and neck, 9 and non-small-cell lung cancer;10 neuroendocrine tumors;11 metastases of unknown primary origin;12 and non-Hodgkin’s lymphoma. 13 The ability of FDG-PET to visualize tumors is based on the increased carbohydrate metabolism of malignant cells, with subsequent elevated glucose utilization and selective 18FDG uptake. Once phosphorylated by hexokinase, FDG accumulates intracellularly because it cannot be metabolized as glucose. Although well-differentiated thyroid malignancies with sufficient 131I uptake are associated with decreased glucose metabolism, and in contrast, dedifferentiated tumors lacking the possibility of 131I accumulation show elevated glucose utilization, FDG-PET has been also introduced in the follow-up of thyroid cancer. 14–17 Our study assesses the experience with FDG-PET in the detection of recurrent thyroid carcinoma in the presence of a negative 131I scan and pathologic serum thyroglobulin values.

Background. Patients with well-differentiated thyroid cancer (WDTC) regularly have an excellent prognosis. However, tumor recurrence either involving the thyroid bed or the regional lymph nodes, or both, can be associated with significant morbidity and even mortality. The aim of the follow-up after primary surgery is to detect recurrent disease at its earliest stage. We assessed the value of different diagnostic methods in detecting locoregional recurrence in patients with WDTC. Methods. We prospectively identified 150 patients with WDTC. Of those, 43 (28.7%) presented with recurrent disease. Ultrasonography -guided fine needle biopsy (US-FNB), iodine 131 ( 131 I) wholebody scintigraphy, thyroglobulin (Tg) measurement, and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) were carried out. Results. Ultrasonography detected malignant lesions in 95.3% of the patients. The true positive rate of US-FNB was 95.3%. 131 I scanning had true positive, false negative, and false positive results in 54.2%, 40.0%, and 5.7% of the cases, respectively. In 85.7% of the patients, Tg levels were within pathologic range. Among the 13 patients who underwent FDG-PET, 84.6% showed pathologic uptake indicating malignancy. US and US-FNB provided the highest specificity for detecting recurrence ( P Conclusions. In patients with WDTC and locoregional recurrence, US and US-FNB are the most sensitive methods in detecting local recurrence or regional lymph node metastases. FDG-PET is valuable in case of negative 131 I scanning results and elevated serum Tg levels. The method has limitations in finding minimal disease. (Surgery 2000;128:1067-74.)

The early detection of metastases from medullary thyroid cancer (MTC) is important because the only curative therapy consists in surgical removal of all tumour tissue. There is no single sensitive diagnostic imaging modality for the localization of all metastases in patients with MTC. Therefore, in many cases several imaging modalities (e.g. ultrasonography, magnetic resonance imaging, computerized tomography and scintigraphy using pentavalent technetium-99m dimercaptosuccinic acid, thallium-201 chloride, indium-111 pentetreotide, anti-CEA antibodies or metaiodobenzylguanidine) must be performed consecutively in patients with elevated calcitonin levels until the tumour is localized. In this prospective study, we investigated the value of fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in the follow-up of patients with MTC. [18F]FDG PET examinations of the neck and the chest were performed in 20 patients with elevated calcitonin levels or sonographic abnormalities in the neck. Positive [18F]FDG findings were validated by histology, computerized tomography or selective venous catheterization. [18F]FDG PET detected tumour in 13/17 patients (nine cases were validated by histology, four by computerized tomography). Five patients showed completely negative PET scans (of these cases, one was true-negative and four false-negative). One patient with [18F]FDG accumulation in pulmonary lesions from silicosis and one patient with a neck lesion that was not subjected to histological validation had to be excluded. Considering all validated localizations, [18F]FDG PET detected 12/14 tumour manifestations in the neck, 6/7 mediastinal metastases, 2/2 pulmonary metastases and 2/2 bone metastases. In two patients with elevated calcitonin levels, no diagnostic modality was able to localize a tumour. The sensitivity of [18F]FDG PET in the follow-up of MTC was 76% (95% confidence interval 53%–94%); this is encouraging. [18F]FDG PET promises to be a valuable diagnostic method, especially for the detection of lymph node metastases, surgical resection of which can result in complete remission.

Fine-needle aspiration biopsy (FNAB) is a simple technique for the investigation of suspicious thyroid nodules. However, low success rates are reported in the literature. The aim of this prospective study was to compare the clinical performance and impact of an automatic aspirator, referred to here as Aspirator 3, to those of the manual technique for the FNAB of clinically suspicious thyroid nodules.One hundred nine consecutive patients with 121 clinically suspicious thyroid nodules underwent a biopsy twice of the same site with the clinically approved Aspirator 3 and with the manual technique. The number of follicular cell formations and the total number of follicular cells in the aspirate were counted using the ThinPrep® method.With the Aspirator 3, the total number and the mean number of extracted cell formations were significantly higher than the values achieved with the manual technique (total: 3222 vs. 1951, p=0.02; mean: 27 vs. 16). The total number of cells that were biopsied was also higher when the Aspirator 3 was utilized (47,480 vs. 23,080, p=0.005). Overall, the Aspirator 3 was superior in 65 biopsies, and the manual technique was superior in 39 biopsies.In terms of cell formations and the total number of cells aspirated, the Aspirator 3 was superior to the manual technique. Further, the Aspirator 3 was more convenient to use and had a greater precision in needle guidance.

Advanced tumour stage and initial metastases are associated with reduced general and tumour-free survival in patients with differentiated thyroid carcinoma. Optimal initial therapy is mandatory for a positive patient outcome, but can only be performed if all non-iodine-avid tumour lesions are known before planning treatment. We analysed the benefit of (18)F-FDG PET/CT at initial diagnosis in patients with high-risk differentiated thyroid carcinoma and determined whether the (18)F-FDG PET/CT results led to a deviation from the standard procedure, which consists of two consecutive radioiodine treatments with thyroid hormone suppression in between and no additional imaging, with individual patient management.The study group comprised 90 consecutive patients with either extensive or metastasized high-risk differentiated thyroid carcinoma who received (18)F-FDG PET/CT after the first radioiodine treatment approximately 4 weeks after thyroidectomy under endogenous TSH stimulation. We carried out PET/CT imaging with low-dose CT without contrast medium, which we only used for attenuation correction of PET images.(18)F-FDG PET/CT was positive in 26 patients (29%) and negative in 64 patients (71%). Compared to the results of posttherapeutic (131)I whole-body scintigraphy, the same lesions were PET-positive in 7 of the 26 patients, different lesions were PET-positive in 15 patients, and some PET-positive lesions were the same and some were different in 4 patients. TNM staging was changed due to the PET results in 8 patients. Management was changed in 19 of the 90 patients (21%), including all patients with only FDG-positive lesions and all patients with both FDG-positive and iodine-positive lesions. Age was not a predictive factor for the presence of FDG-positive lesions. FDG-positive and iodine-positive lesions were associated with high serum thyroglobulin. However, at low serum thyroglobulin values, tumour lesions (iodine- and/or FDG-avid) were also diagnosed. Thus, the serum thyroglobulin value prior to the first radioiodine treatment cannot be used as a predictor of the presence of FDG-positive lesions.(18)F-FDG PET/CT resulted in a change of therapeutic procedure in 11 of 90 patients and in a change of patient management through additional diagnostic measures in 8 of 90 patients, and is consequently very helpful in initial staging. At our hospital, (18)F-FDG PET/CT in high-risk patients with differentiated thyroid carcinoma has been established as an initial staging modality.

Summary Purpose: This study evaluated the impact of 124I-positron emission tomography (PET) dosimetry on post-primary surgery therapy in radioiodine-naive patients with advanced differentiated thyroid cancer (DTC). Patients, material, methods: In each of 28 thyroidectomized patients with high-risk DTC (one or more of pT4, pN1 or pM1), we gave 23.50 MBq of 124I as an oral capsule and performed PET dosimetry to calculate the individualized therapeutic 131I activity that would, insofar as possible, achieve a radioiodine dose ≥100 Gy to all metastases without exceeding 2 Gy to the blood (a surrogate for bone marrow toxicity). We thus determined the absorbed lesion dose per GBq of administered 131I activity (LDpA) based on serial PET (4, 24, 48, 72 and 96 h after oral 124I intake) and PET/computed tomography (25 h after 124I intake) and the critical blood activity (CBA) based on blood and whole-body radiation counting (2, 4, 24, 48, 72, 96 h after 124I intake). We compared the dosimetry-based interventions with our standard empirical protocol. Results: 25 patients had a total of 126 iodine-positive metastases. 18 (72%) of the 25 had solely iodine-avid metastases, while seven (28%) had both iodine- avid and -non-avid metastases. In two patients (8%), none of the iodine-avid metastases could have been practically treated with a sufficient radiation dose. Relative to the empirical protocol, 124I-PET dosimetry findings changed management in 7 (25%) patients, e. g. allowing application of activities >11 GBq 131I. Further changes included implementation of hematological back-up in a patient found to be at risk of life-threatening marrow toxicity, and early multimodal therapy in 9 (32%) patients. Conclusion: 124I-PET dosimetry is a useful routine procedure in advanced DTC and may allow safer or more effective radioiodine activities and earlier multimodal interventions than do standard empirical protocols.

In patients with acromegaly, the exact incidence of thyroid disorders is still controversial and less is known about the impact of disease activity and successful treatment. To address this issue, we investigated 73 acromegalic patients (age 55 +/- 13 yr; mean +/- SD) by ultrasonography in comparison to an age-matched control group (54 +/- 1 yr) in the same moderate iodine deficient area (retrospective study). These non-acromegalic volunteers (n = 199) were examined in the same clinic during a thyroid screening test. At the time of examination, 52 (71.2 %) of the acromegalic patients were active, 17 (23.3 %) were cured, and 4 (5.5 %) were controlled with somatostatin analogues. The prevalence of goiter (normal range < 18 ml female, < 25 ml male) was significantly higher (82.2 %) in the mixed group of acromegalics (active, well controlled, cured; n = 73) and in the active group (90.4 %) than in the control group (n = 199, 18.1 %, p < 0.001). Thyroid nodules were found in 63.0 % of the mixed group of acromegalics and in 71.2 % of patients with active disease (33.1 % in controls, p < 0.001). (99 m)Tc scintigraphy revealed thyroid autonomy in 9/73 (12.3 %) and cold nodules in 19/73 (26.0 %) patients. Thyroid cancer was diagnosed in 4 (5.5 %) of acromegalic patients (3 papillary and 1 follicular carcinoma). We found a weak correlation between the disease duration and the initial thyroid volume (r = 0.54, p < 0.0056). Thirty-seven newly diagnosed acromegalics were followed over a period of 7.3 +/- 4.1 years. 5 (13.5 %) of these patients remained active, 8 (21.6 %) were controlled with somatostatin analogues, and 24 (64.9 %) were cured. The mean age, sex distribution, disease duration, prevalence of TSH-deficiency, and initial thyroid volume (46 +/- 11 ml in active, 42 +/- 7 ml in controlled, and 45 +/- 5 ml in cured patients) did not differ statistically between the three groups. In patients with active acromegaly, thyroid volume increased by 19.5 +/- 8.1 %. In contrast, thyroid volume decreased in the group of medically controlled and cured acromegalics (- 21.5 +/- 7.1 %; p < 0.005 and - 24.2 +/- 5.7 %; p < 0.002, respectively). No correlation was found between thyroid volume and TSH levels, levothyroxine and/or iodide administration neither in TSH sufficient nor in TSH insufficient patients. In conclusion, successful treatment of patients with active acromegaly decreases thyroid volume. Cold nodules and thyroid cancer frequently occur in acromegalic patients.