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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.

SummaryIn this study we evaluated the success rate of double fine needle aspiration biopsy (FNAB) of clinically suspicious thyroid nodules in one session. Aim: The success rate of FNAB in clinical setting is quite low. There were several attempts made to improve the success rate of this method. It is anticipated that a double FNAB in one session would increase the success rate of FNAB. Patients, methods: 176 consecutive patients (130 women, 46 men; mean age 56 years ± 11) with at least one clinically suspicious nodule were included in this study. Each individual nodule was biopsied twice (20G- and 21G-needle). In 33 patients, two suspicious nodules were biopsied, accounting for a total of 209 biopsied thyroid nodules. To evaluate the success rate the number of cell formations and the total number of cells in each cell formation were counted. Results: The biopsy with the 20G needle provided in mean 40 cell cluster with a mean of 830 cells niedwhereas the 21G needle provided in mean 41 cell cluster with a mean of 1010 cells. With the 20G needle the success rate was 73%, with the 21G needle 78% and the combination of the both biopsies provided a success rate of 87% (p = 0.01). Based on the number of cell formations and the total number of cells, the difference between the two needle sizes was not significant (p = 0.5 for cell formations and p = 0.9 for the total number of cells, respectively). Conclusion: A double FNAB of suspicious thyroid nodules in one session provides a higher success rate, and a 21G needle is sufficient enough.

Ziel: Calcitonin (hCT) ist ein entscheidender diagnostischer Parameter beim medullaren Schilddrusenkarzinom (MTC). Verschiedene immunometrische Assays wurden untersucht, um Einfluss auf den hCT-Zielbereich fur so genannte „biochemisch geheilte“ MTC-Patienten zu prufen. Patienten, Methodik: Mit sechs Assays [Nichols ICMA, Biomerica IEMA, Immulite 2000 (Siemens), Calcitonin-IRMA magnum (Medipan), SELco-IRMA (Medipan) und Calcitonin IRMA (Medgenix)] haben wir als Modell fur kurativ behandelte MTC-Patienten basale hCT-Werte von 198 thyreoidektomierten Patienten mit differenziertem Schilddrusenkarzinom (DTC) und Pentagastrintest-stimulierte Werte bei 13 DTC- und 13 kurativ behandelte MTC-Patienten, bestimmt. Ergebnisse: Die basalen hCT-Werte der thyreoidektomierten DTC-Patienten waren beim Nichols ICMA (n = 138) und Immulite 2000 (n = 60) in 100%, Biomerica IEMA (n = 57) in 97%, IRMA magnum (Medipan) (n = 20) in 85% der Falle unterhalb der Nachweisgrenzen (NWG), beim SELco-IRMA (n = 20) und Medgenix IRMA (n = 76) dagegen uberwiegend im Bereich Schilddrusengesunder. Beim Nichols ICMA und Immulite 2000 lagen die Werte der Pentagastrintests bei 13 DTC-Patienten und 9/13 MTC-Patienten auch im Verlauf unter der NWG. Bei vier MTC-Patienten, die (auch bei negativen basalem hCT) eine hCT-Stimulierbarkeit zeigten, liesen sich im spaten Verlauf Rezidive nachweisen. Schlussfolgerungen: Bei Assays mit hoher Monomer-Spezifitat (Nichols-ICMA, Biomerica IEMA, Immulite 2000, eingeschrankt IRMA magnum) sind fur die Definition „biochemisch geheilte“ MTC-Patienten basale und Pentagastrin-stimulierte hCT-Werte unter der NWG zu fordern. Bei Assays mit geringerer Monomer-Spezifitat (SELco-IRMA, IRMA Medgenix) sind Werte innerhalb der Referenzbereiche Schilddrusengesunder noch kompatibel mit „biochemischer Heilung“.

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.

In recent years, various professional societies published guidelines for diagnostic evaluation of thyroid nodules, in which the indication for scintigraphy is restricted to patients with subnormal TSH values. It is seen controversial whether such recommendations should be transferred to Germany, partly because of lower iodine intake in this country and the consequent higher percentage of autonomous thyroid nodules, which are not accompanied by a measurable dysfunction. Since reliable data to this topic are scarce, we analyzed multicentrically the spectrum of scintigraphically "hot" and "warm" nodules under the current epidemiological conditions.In 10 German nuclear medicine out-patient institutions we evaluated the diagnostic data from a total of 514 patients, in whom unequivocally hyperfunctional nodules (focal increased uptake in comparison to perinodular tissue with a sonographically nodular correlative ≥1 cm) could be detected by (99m)Tc-pertechnetate scintigraphy. To minimize selection bias, the surveys were not carried out in hospitals.The recorded parameters included the thyroid hormone levels, the global (99m)Tc-uptake (TcTU), the size of each nodule and the total autonomous nodular volume (V(aut)).Only 20% of the patients with "hot" nodules had subnormal TSH levels (0.1 to 0.33 mU / l), the remaining patients had TSH levels from 0.34 to 3.5 mU /l (in one third of the patients TSH levels even exceeded 1.0 mU/l). Moreover, we found no relevant correlation between TSH and TcTU or V(aut).In Germany, in at far the largest proportion of patients with autonomous thyroid nodules objectified by means of scintigraphy, TSH levels are within the normal range. Since such nodules with maximum safety can be classified as benign, a corresponding scintigraphic finding has a high priority for the patient. These current data support that it is not reasonable to restrict scintigraphy to patients with subnormal TSH values in this country.

Twenty-two patients (mean age 61) with metastasizing, progressive, nonradioiodine-accumulating thyroid carcinoma of the follicular epithelium were treated with doxorubicin between 2000 and 2005. Tumors were histologically classified as follicular in 15 patients (68%) and papillary in 7 patients (32%). In addition, nine patients (mean age 51 years) with medullary thyroid carcinoma were treated with doxorubicin between 1997 and 2005. Treatment consisted of doxorubicin: either 8 cycles of 15 mg/m2 weekly or 3 cycles of 60 mg/m2 every 3 weeks, repeated once, depending on response and side effects. The effect of therapy was evaluated by radiographic imaging, [18F] FDG-PET, and bone scans. In patients with papillary or follicular thyroid carcinoma, 5% had a partial regression over 6 months, 42% had stable disease for a median of 7 months (range: 1-22), and 53% had continuous progression established over 5 months (range: 1-11). Three patients died before completing chemotherapy. In patients with medullary thyroid carcinoma, 11% had a partial regression over 6 months followed by stable disease for 3 months, 11% had stable disease over 7 months, and 79% demonstrated progressive disease established over 5 months (range: 2-12). Doxorubicin can be a valid chemotherapy option, especially for advanced or metastatic thyroid carcinoma of the follicular epithelium.

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.

Depression and anxiety are the most common mental symptoms in patients with thyroid cancer (DTC) and have an important influence on the quality of life. The aim of the current study was to identify protective factors of depression and anxiety in DTC patients.In a cross-sectional study 230 DTC patients were examined with Hospital Anxiety and Depression Scale (HADS-D), the Sense of Coherence Scale (SOC-13) and the Questionnaire of Social Support (F-SOZU).Depression correlated highly significantly with anxiety (r = .633, p = 0,001). Social support and sense of coherence correlated highly significantly negative with depression as well as with anxiety (both por = 0,001). Although still significant, the correlation between age and anxiety was lower (r = -.19; por = 0,005). The TSH level as an indicator of hypothyreodism did not correlate with depression or with anxiety on a significant statistical level. Furthermore, variables such as education, religiosity and elapsed time interval since initial diagnosis were not correlated with depression and anxiety.Our results support the thesis that low social support and low sense of coherence enhance vulnerability to depressive and anxiety symptoms.

Carriers of the C allele of the common C825T polymorphism in the GNB3 gene of the G protein have been associated with the development of follicular thyroid adenomas. Since the C allele of this polymorphism is related to a lower signalling capacity, it was speculated whether the C825T polymorphism may play a particular role in oncocytic thyroid tumours, which are recognized for their reduced ability to synthesize thyroid-specific proteins and hormones, although they possess an intact thyroid-stimulating hormone receptor–adenylyl cyclase system. Using pyrosequencing, both the genotype distribution and the allele frequency of the C825T polymorphism were investigated in a series of 104 patients with oncocytic thyroid tumours of follicular cell origin [58 adenomas, 41 follicular thyroid carcinomas (FTCs), and five papillary thyroid carcinomas (PTCs)]; the results were compared with those obtained from 321 age and gender-matched healthy blood donors and a series of 327 non-oncocytic thyroid tumours of follicular cell origin (119 adenomas, 80 FTCs, and 186 PTCs). Analysis of the genotype distribution (comparing oncocytic with non-oncocytic tumours of the present series) revealed a significantly increased odds ratio (OR) for CC versus TT (OR = 4.22; p = 0.011) and CC versus CT (OR = 1.62; p = 0.049) carriers to develop an oncocytic thyroid tumour; ORs to develop an oncocytic thyroid tumour were also increased comparing the genotype distribution between the group of oncocytic tumours and healthy controls for CC versus TT (OR = 3.73; p = 0.017) and CC versus all T carriers (OR = 1.56; p = 0.034). Oncocytic thyroid tumours as a group showed a statistically significant increase of the C-allele frequency when compared with all non-oncocytic tumours (p = 0.0039) as well as healthy blood donors (p = 0.017). The results strongly suggest that the C allele of the GNB3 C825T polymorphism of the G protein β3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours. This polymorphism may thus be considered a (co)factor favouring the development of oncocytic thyroid tumours, although the biological mechanism(s) underlying this association remain obscure. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Scintigraphy of the hyperfunctioning parathyroid glands using technetium 99m ((99m)Tc)-methoxyisobutylisonitrile ((99m)Tc-MIBI) is an established and highly sensitive preoperative localization tool whose importance has been further increased by advances in minimally invasive surgery . The goal of the present prospective study was to determine the benefit of optimized imaging in a consistent patient population.Eighty-four patients with first presentations of primary hyperparathyroidism were investigated with (99m)Tc-MIBI scintigraphy, thyroid scintigraphy, and cervical ultrasonography. The evaluation algorithm consisted of (a) evaluation of the planar images alone, (b) additional evaluation of single-photon emission computed tomography (SPECT), (c) additional evaluation of thyroid gland scintigraphy, and (d) additional evaluation of ultrasound. All patients subsequently underwent parathyroidectomy. The intraoperative and the histologic findings were correlated with the results of the scintigraphic imaging.The sensitivity of planar parathyroid scintigraphy was 74% and could be increased to 91% by the additional investigations. The difference was statistically significant (p0.05). At the same time, a small increase in specificity from 96% to 99% was seen.Prior to minimally invasive treatment of hyperparathyroidism, we recommend combined localization studies consisting of sequential (99m)Tc-MIBI scintigraphy, additional SPECT plus thyroid gland scintigraphy, plus high-resolution cervical ultrasonography.

In verschiedenen Tumorentitaten ist die Uberexpression von c-erbB-2 ein potenzieller Marker fur aggressives biologisches Verhalten. Ziel unserer Untersuchung war die c-erbB-2 Uberexpression mit dem klinischen Verlauf zu korrelieren und die Bedeutung von c-erbB-2 bei papillaren Schilddrusenkarzinomen zu untersuchen. Patienten, Methoden: 32 Patienten mit papillaren Schilddrusenkarzinomen wurden in einer zweischrittigen immunozytochemischen Farbungsprozedur unterzogen (DAKO HercepTest). Es folgte eine semiquantitative Evaluation auf Basis der Farbungsintensitat und des Prozentanteils der betroffenen Tumorzellen. Die immunhistochemischen Daten wurden mit den Follow-up-Daten korreliert. Ergebnisse: 34% (11/32) der Patienten zeigten eine mebranose Uberexpression des c-erbB-2-Onkoproteins. Die Korrelation mit den klinischen Daten zeigte, dass 81% (9/11) der c-erbB- 2-positiven Patienten und nur 33% (7/21) c-erbB-2-negative Patienten ein Tumorrezidiv entwickelten (p = 0,02). 3/11 c-erbB-2-positive Patienten starben an der Tumorerkrankung, wahrend alle c-erbB-2-negativen Patienten noch leben (p = 0,03). Schlussfolgerung: Unsere Ergebnisse legen nahe, dass die Uberexpression des c-erbB-2-Onkoproteins in einem Zusammenhang zu dem klinischen Verlauf bei Patienten mit papillarem Schilddrusenkarzinom steht.

Objective: Very few previous studies have compared the degree of health-related quality of life (HRQL), depression and anxiety of differentiated thyroid cancer patients (DTC) under short-term hypothyroid-ism and levothyroxine treatment. Methods: Using patient-completed instruments, we examined the frequency of physical complaints, HRQL, anxiety and depression in 130 DTC patients hospitalized for radioiodine therapy or whole-body diagnostics (age 52 years, female 71%) under short-term hypothyroidism (4 weeks of levothyroxine withdrawal; DTC-H) and in 100 DTC out-patients under TSH-suppressive doses of levothyroxine subsequent to radioiodine therapy (DTC-L; age 49 years, female 81%). Results: Compared with the German general population, DTC-H as well as DTC-L patients had significantly impaired HRQL. Notably, the decrease in HRQL was significantly higher in DTC-H than in DTC-L patients. Surprisingly, the prevalence of anxiety (44.6%) but not depression (17.7%) was much higher in the DTC-H patients than in the general population. In contrast to expectations, similar results for anxiety (44.0%) and depression (17.6%) were observed in the DTC-L patients. Conclusions: This mounting evidence suggests that a consistent pattern of HRQL impairment is experienced by patients with DTC. The high frequency of anxiety and the significantly reduced HRQL should be considered in the aftercare of DTC patients.

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.

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone (P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.

Today, positron emission tomography (PET) investigation using fluorodeoxyglucose (FDG) is the most sensitive and specific single modality established for localizing metastases of medullary thyroid cancer (MTC). Even at calcitonin serum levels below 20 pg/ml, tumour localization may be successful in individual cases. However, especially in such early tumour stages, the morphological correlation using PET is unsatisfactory. With the newly available fixed combination of PET and computed tomography (PET/CT), this drawback can be overcome as PET/CT allows a point-by-point correlation of pathological function with morphological structure. Conventional PET alone yielded an approx 80 % sensitivity and specificity in MTC: a result that will be surpassed by the combined PET/CT scanner.

Die Tumoren der Schilddruse sind fast ausschlieslich epithelialer Natur. Wahrend das Adenom der Schilddruse ein durchaus haufiger Tumor ist, machen die Karzinome der Schilddruse nur etwa 1% aller menschlichen Malignome aus. Die differenzialdiagnostische Problematik der Unterscheidung Adenom—Karzinom sowie eine Reihe von Varianten und Besonderheiten dieser Tumoren bereiten dem Pathologen regelmasig betrachtliche Probleme. Der folgende Ubersichtsartikel ist der Versuch, einen Leitfaden fur die histologische Begutachtung von Schilddrusentumoren in der taglichen Routinetatigkeit zu geben. Besonderen Stellenwert wird der standardisierten Aufarbeitung der Schilddrusenoperationspraparate, einem zielgerichteten diagnostischen Vorgehen, dem Einsatz der Immunhistochemie in der Schilddrusenpathologie sowie dem intraoperativen Gefrierschnitt der Schilddruse eingeraumt.

Die haufigsten morphologischen Veranderungen der Schilddruse in der taglichen Diagnostik betreffen Hyperplasien der Follikelepithelien (Struma). Der folgende Ubersichtsartikel beschaftigt sich mit der Atiologie, Epidemiologie und Klinik der verschiedenen Formen der Struma sowie deren morphologischer Abgrenzung gegenuber dem Adenom der Schilddruse. Aus der Hyperplasie der kalzitoninproduzierenden C-Zellen in ihrer neoplastischen Form gehen die familiaren medullaren Schilddrusenkarzinome hervor. Der 2. Teil dieses Artikels beschaftigt sich mit der Definition der neoplastischen C-Zell-Hyperplasie und ihrer Unterscheidung von der physiologischen C-Zell-Hyperplasie.

Differentiated thyroid cancer is a malignant tumour that has a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery, radioiodine therapy and TSH suppressive medication is of proven efficacy. However, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumour grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumours may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy. Retinoic acids have been shown to exert re-differentiating effects on thyrocytes in various experimental studies and case reports, and it was on this basis that this pilot study was initiated. Patients with advanced thyroid cancer and without the therapeutic options of operation or radioiodide therapy were treated with 13- cis-retinoic acid at a dosage of 1.5 mg/kg body weight daily over 5 weeks. Parameters for assessment of the therapeutic effect were serum thyroglobulin (TG) levels, radioiodine uptake, and tumour size prior to and after retinoid treatment. Fifty patients were evaluated for response, classified as reduction in tumour size and TG levels, stable disease or disease progression. Thirteen patients showed a clear increase in radioiodine uptake, and eight a mild increase. TG levels were unchanged or decreased in 20 patients. Tumour size was assessable in 37 patients; tumour regression was observed in six, and there was no change in 22. In total, a response was seen in 19 patients (38%). Response to retinoid therapy did not always correlate with increased radioiodine uptake, so other direct antiproliferative effects have to be assumed. The encouraging results of the study and the low rate of side-effects with good tolerability of retinoids warrant further studies with altered inclusion criteria and employment of other redifferentiating drugs or combinations of agents.

The aim of this study was to investigate the impact of analytical aspects on the clinical usefulness of calcitonin (CT) measurement. In a retrospective analysis, CT levels measured by a polyclonal immunometric assay (Scantibodies Laboratory, CA, USA) were evaluated in various clinical situations. CT in newly diagnosed medullary thyroid cancer (MTC) (n = 20) ranged from 15.5-87130 pg/ml (median 661 pg/ml). Levels10 pg/ml were seen in 7.3% of 314 patients with benign nodules, 48.9% of 45 patients with impaired kidney function, 97.7% of 87 patients on hemodialysis, 30.2% of 43 patients after renal transplantation, and in 71.0% of 31 patients with critical illnesses. Subgroups of patients were reevaluated by two monoclonal immunometric assays specific for mature CT. CT levels measured by the monoclonal immunometric assays were highly correlated to the polyclonal assay results in MTC patients, but were significantly different with a lower incidence of elevated levels in patients with renal disease and critical illnesses. In conclusion, highly sensitive assays with cut-off values of 10 pg/ml or below are mandatory for CT screening in nodular thyroid disease. The specificity of CT measurement in patients with renal disease and critical illnesses is higher with monoclonal assays specific for monomeric CT. These methodological aspects have to be regarded if CT measurement is used for decision making in nodular thyroid disease.

Despite the fact that several recent studies report an expression of somatostatin receptors in nonmedullary thyroid cancer (non-MTC), there is still no consensus concerning the diagnostic and therapeutic usefulness of radionuclide-labeled somatostatin analogues in non-MTC. We present the results of 50 scintigraphic studies with (111)In-Pentetreotide ((111)In-P) in 48 patients with metastasizing non-MTC (n = 9 papillary, n = 9 follicular, n = 29 Hurthle cell, n = 1 insular carcinoma). The findings were compared with histology and with other imaging modalities. (111)In-P provided unequivocally positive results in 37 of 50 (74%) of the patients (27% in the 11 patients with current thyroglobulin levels10 ng/mL and 85% in the patients with thyroglobulin10 ng/mL). Histopathology demonstrated that maximal uptake was observed in Hurthle cell carcinoma (95% positive examinations if thyroglobulin exceeds 10 ng/mL). We also describe for the first time dosimetric and clinical data from the courses of 90Y-DOTATOC therapy in three patients with progressive, somatostatin-receptor-positive non-MTC (up to 9.3 GBq per 4 cycles). Tumor progression could not be stopped in any of the patients treated with 90Y-DOTATOC. We conclude that (111)In-P is a promising tool for whole-body diagnosis in nonradioiodine-accumulating non-MTC, especially in Hürthle cell cancer, and if 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is not available. Although the number of patients treated with 90Y-DOTATOC is still limited, our applied treatment protocol appears to be ineffective in metastasizing non-MTC.

Determination of thyrotropin (TSH) by sensitive immunometric assays is currently judged as the most sensitive and also most cost-effective first-line approach to thyroid function testing. Further improvement of assay sensitivity has led to the description of third generation TSH assays with a functional sensitivity in the range of 0.01 to 0.02 mU/l. In the present study, we analyzed interassay precision profiles of a commercially available third generation assay (ACS:180 TSH-3) and documented the critical role of the time span used for the assessment of a method's functional sensitivity. By using a standardized approach with five serum pools measured in 30 different runs across a 6-week period, functional sensitivity was calculated as 0.015 mU/l. The TSH concentrations measured by two different third generation assays (ACS: 180 TSH-3 and Elecsys TSH) in samples from healthy blood donors were highly correlated (r = 0.76, n = 252). In some samples, however, discordant results were obtained. Euthyroid reference intervals were determined as 0.30-3.68 mU/l for the ACS:180 TSH-3 assay and as 0.36-3.64 mU/l for the Elecsys TSH assay. Reevaluation of reference intervals including only TPOAb or TgAb negative samples resulted in almost the same reference ranges. Measuring TSH concentrations in various patient populations, third generation assay turned out to be advantageous in the following clinical situations. (a) In patients with mildly suppressed but well detectable TSH concentrations due to functional thyroid autonomy (0.03-0.3 mU/l), overt hyperthyroidism can be excluded by third generation TSH measurement alone without the need of additional thyroid hormone measurements; (b) in patients receiving long term suppressive T4 treatment after thyroidectomy for differentiated thyroid cancer, measurement of basal TSH by third generation assays allow accurate monitoring of hormone therapy without the need for TRH testing; (c) in most patients with severe nonthyroidal illnesses and decreased TSH levels, TSH concentrations measured by third generation assays are only moderately suppressed and can be clearly discriminated from undetectable levels in overt hyperthyroidism. In conclusion, the use of third generation TSH assays is recommended in specialized clinical laboratories frequently analyzing samples taken in one of those clinical situations.

CT (top), 124I-PET (middle) and co-registered 124I-PET/CT (bottom) show the exact localisation of four iodine-avid metastases of follicular thyroid carcinoma in the mediastinum L.S. Freudenberg (✉) Clinic and Policlinic for Nuclear Medicine, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany e-mail: l.freudenberg@t-online.de Tel.: +49-201-7232032, Fax: +49-201-7235964 Image of the month