Longer-term recurrence rate after low versus high dose radioiodine ablation for differentiated thyroid Cancer in low and intermediate risk patients: a meta-analysis.

BACKGROUND: Regarding the longer-term recurrence rate the optimal activity for the remnant thyroid ablation in patients with differentiated thyroid cancer (DTC) is discussed controversially. For the short-term ablation success rate up to 12 months there are already several meta-analyses. In this study we performed the first meta-analysis regarding the longer-term recurrence rate after radioactive 131-I administration. METHODS: We conducted an electronic search using PubMed/MEDLINE, EMBASE and the Cochrane Library. All randomized controlled trials (RCTs) assessed the recurrence rate after radioactive iodine ablation in patients with DTC, with a follow-up of at least two years were selected. Statistics were performed by using Review Manager version 5.3 and Stata software. RESULTS: Four RCTs were included in the study, involving 1501 patients. There was no indication for heterogeneity (I2 = 0%) and publication bias. The recurrence rate among patients who had a low dose 131-iodine ablation was not higher than for a high dose activity (odds ratio (OR) 0.93 [95% confidence interval (CI) 0.53-1.63]; P = 0.79). The mean follow-up time was between 4.25 and 10 years. The subgroup analysis regarding the TSH stimulated thyroglobulin values (< 10 ng/mL versus < 2 ng/mL versus ≤1 ng/mL) showed no influence on recurrence rate. CONCLUSIONS: For the first time we showed that the longer-term, at least 2-year follow-up, recurrence rate among patients who had 131-iodine ablation with 1.1 GBq was not higher than with 3.7 GBq.

Correction for hyperfunctioning radiation-induced stunning (CHRIS) in benign thyroid diseases.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.000001) of the fluctuation range of the results received with CHRIS. Similar results were obtained in the subgroup of patients with multifocal autonomous nodules. The mean value of the administered dose calculated with the conventional Marinelli equation was 131 Gy and therefore significantly below the CHRIS-calculated radiation dose of 150 Gy (p < 0.05). Again, the fluctuation range of the CHRIS-calculated radiation dose in the target volume was significantly improved compared with the conventional Marinelli equation (p < 0.000001). CONCLUSIONS: With the presented CHRIS equation it is possible to calculate a required individual stunning-independent radioiodine activity for the first time by only using data from the radioiodine uptake testing. The results of this study deepen our understanding of thyroid stunning in benign thyroid diseases and improve precision of dosimetry in radioiodine-131 therapy of goiter and multifocal autonomous nodules.

Lowest effective 131I activity for thyroid remnant ablation of differentiated thyroid cancer patients. Dosimetry-based model for estimation.

AIM: A theoretical dosimetry-based model was applied to estimate the lowest effective radioiodine activity for thyroid remnant ablation of low-risk differentiated thyroid cancer patients. PATIENTS, METHODS: The model is based on the distribution of the absorbed (radiation) dose per administered radioiodine activity and the absorbed dose threshold of 300 Gy for thyroid remnants, the level believed to destroy most thyroid remnants. For this purpose, ¹²4I PET/CT images of 49 thyroidectomised patients were retrospectively analysed to measure the distribution of the (average) absorbed doses to thyroid remnant per administered ¹³¹I activity. The fraction of thyroid remnants that received at least 300 Gy was determined for standard activities between 0.37 and 5.55 GBq. The lower activity was considered to be equally effective to that obtained with higher activity if the (absolute) fraction difference was below 5%. RESULTS: A total of 62 thyroid remnants were included. The medians and ranges (in parentheses) for the absorbed dose per unit 131I activity were 359 Gy/GBq (34 to 1825 Gy/GBq). The fractions of thyroid remnants receiving more than 300 Gy at different therapy activities (within parentheses) were 60% (1.11 GBq), 76% (1.85 GBq), 79% (2.22 GBq), and 81-82% for activities between 2.59 and 3.70 GBq. The therapy activity of 1.11 GBq is considerably less effective than that of 1.85 or 2.22 GBq; therapy activities were equally effective in the range between 2.22 to 3.70 GBq. CONCLUSION: On the basis of the model and the patients' data included, the lowest effective therapy activity appears to be approximately 2.2 GBq to ablate thyroid remnants. The results of this study may help to guide the design of prospective clinical studies.

Expression of the cAMP binding protein EPAC1 in thyroid tumors and growth regulation of thyroid cells and thyroid carcinoma cells by EPAC proteins.

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.

Diagnosis of hyperfunctional thyroid nodules: impact of US-elastography.

AIM: 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 significant 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.

Success rate of repeated fine needle aspiration biopsy of clinically suspicious thyroid nodules.

UNLABELLED: In 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 whereas 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.

[Influence of the calcitonin assay on the definition of biochemical cure in patients with medullary thyroid carcinoma]. / Assay-Abhängigkeit der Calcitonin-Zielbereiche für "biochemisch geheilte" Patienten mit medullärem Schilddrüsenkarzinom.

AIM: Calcitonin (hCT) is an important diagnostic parameter in medullary thyroid carcinoma (MTC). We determined the variability of the reference ranges of several currently available immunometric assays for "biochemically cured" MTC patients. PATIENTS, METHODS: We compared six assays [Nichols ICMA, Biomerica IEMA, Immulite 2000 (Siemens), Calcitonin-IRMA magnum (Medipan), SELco-IRMA (Medipan) and Calcitonin IRMA (Medgenix)] in subgroups of 198 patients with differentiated thyroid cancer (DTC) after total thyroidectomy as a model for curatively treated MTC patients. In addition, hCT was measured after pentagastrin stimulation in 13 DTC patients and 13 patients with MTC. RESULTS: The basal hCT concentrations were below the detection limit of the respective assay in 100% of all thyroidectomized DTC patients for Nichols ICMA (n = 138) and Immulite 2000 (n = 60), in 97% for Biomerica IEMA (n = 57), and in 85% for IRMA magnum (n = 20). However, basal hCT was mostly within the reference range in Selco-IRMA (n = 20) and Medgenix IRMA (n = 76). In all DTC patients and 9/13 MTC patients the pentagastrin stimulated hCT was below the detection limit for the Nichols ICMA and Immulite 2000, all four MTC patients with elevated stimulated hCT developed a recurrence during follow-up. CONCLUSIONS: For assays with high monomer specificity (Nichols ICMA, Biomerica IEMA, Immulite 2000, to a lesser degree IRMA magnum) biochemical cure is defined by basal and stimulated calcitonin levels below the detection limit. For assays with low monomer specificity (SELco-IRMA, IRMA Medgenix) calcitonin levels in the reference range of patients without thyroid diseases are consistent with "biochemical cure".

[Optimization of the fine needle aspiration biopsy (FNAB) of thyroid nodules- automatic aspirator versus manual technique]. / Optimierung der Schilddrüsen-Feinnadelpunktion. Automatischer Mikroaspirator versus manuelle Technik.

OBJECTIVE: 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).

Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC.

AIMS: 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 48 h 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 30 mg 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 two-month 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.

Chemotherapy with doxorubicin in progressive medullary and thyroid carcinoma of the follicular epithelium.

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.

Combined metabolic and morphologic imaging in thyroid carcinoma patients with elevated serum thyroglobulin and negative cervical ultrasonography: role of 124I-PET/CT and FDG-PET.

PURPOSE: This study sought to compare iodine-124 positron emission tomography/computed tomography (124I-PET/CT) and 2-[18F]fluoro-2-deoxy-D: -glucose- (FDG-) PET in the detection of recurrent differentiated thyroid carcinoma (DTC) lesions in patients with increasing serum thyroglobulin (Tg), Tg-antibodies, or both, but without pathological cervical ultrasonography. We assessed the lesion detection accuracy of 124I-PET alone, CT alone, (124)I-PET/CT, FDG-PET, and all these modalities combined. MATERIAL AND METHODS: The study included 21 patients (9 follicular, 12 papillary DTC) who had been rendered disease-free by thyroidectomy and radioiodine treatment (RIT) and followed up for 21-275 months after the last RIT. In all patients, FDG-PET was performed first. Within 1 week, 124I-PET/CT was performed 24 h after oral administration of 43 +/- 11 MBq 124I. Imaging results were correlated with further clinical follow-up with (n = 12) or without (n = 9) post-study histology as the reference standard. RESULTS: The sensitivities for DTC lesion detection were: 124I-PET, 49%; CT, 67%; 124I-PET/CT, 80%; FDG-PET, 70%; and all modalities combined, 91%. For local recurrences (distant metastases), the sensitivities were: 124I-PET, 60% (45%); CT, 20% (84%); and FDG-PET, 65% (71%). One-third of lesions demonstrated pathological tracer uptake with both 124I- and FDG-PET, while two-thirds were positive with only one of these modalities. CONCLUSION: Used together, 124I-PET and CT allow localization of foci of highly specific 124I uptake as well as non-iodine-avid lesions. The combination of 124I-PET/CT and FDG-PET improves restaging in recurrent DTC by enabling detection on whole-body scans of local recurrence or metastases that are often not found if only one of the methods or other imaging modalities are applied.

124I-PET dosimetry in advanced differentiated thyroid cancer: therapeutic impact.

PURPOSE: This study evaluated the impact of (124)I-positron emission tomography (PET) dosimetry on post-primary surgery therapy in radioiodine-naïve 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 (124)I as an oral capsule and performed PET dosimetry to calculate the individualized therapeutic (131)I activity that would, insofar as possible, achieve a radioiodine dose >or=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 (124)I 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, (124)I-PET dosimetry findings changed management in 7 (25%) patients, e.g. allowing application of activities >11 GBq (131)I. 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.

The C allele of the GNB3 C825T polymorphism of the G protein beta3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours.

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 beta3-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.

[Evil radioactivity. Subjective perception of radioactivity in patients with thyroid disease prior to treatment with radioiodine]. / Radioaktivität ist böse: Subjektive Konzepte von Radioaktivität bei Schilddrüsenpatienten vor einer möglichen Radioiodtherapie.

AIM: We assess the perspective of patients with thyroid disease towards radiation and radioactivity by means of a cultural-anthropological approach based on qualitative measures and quantitative scores. From the interviews with the patients we evaluate as to how much radioactivity is accepted as an abstract term or as a benefit within the medical context. PATIENTS, METHODS: 68 patients with autonomously functioning thyroid lesions (35 women, 33 men, 32-81 years) were included in this study. All patients were interviewed in an open dialogue with the principal investigator. Patients were asked to describe their attitude towards radioactivity in general and towards radioiodine therapy in particular. Patients were asked to use a scoring system (1 = positive, 5 = negative) to quantify their attitudes. RESULTS: The responses of all patients towards radioactivity in general were heterogeneous with most responses reflecting a negative perception. Many patients expressed their associated fears about atomic energy, malignant diseases and radioactive contamination. The scoring system reflected a mostly negative opinion base. However, patients became more positive once they assumed an immediate benefit of radioactivity for the treatment of their own disease (p = 0.01). CONCLUSIONS: Knowing about significant differences in patient's perception about radioactivity in general or in the clinical context may help to optimise and tailor the initial, pre-therapeutical interview towards the patient.

Development and clinical impact of thyroglobulin antibodies in patients with differentiated thyroid carcinoma during the first 3 years after thyroidectomy.

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 < 10% after 3 years. The median serum half-life of TgAbs in treated DTC patients was 10 weeks. At initial examination (when all patients still had residual thyroid tissue and 17 had metastases), rising TgAb levels were correlated with the inability to detect Tg in 4, 30 and 73% of the patients, when initial TgAbs were < 6, 6-50 or > 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.

Prognostic value of c-erbB-2 expression in papillary thyroid carcinoma.

AIMS: c-erbB-2 overexpression has been shown to be a potential marker of aggressive biological behaviour in a varity of tumours, whereas its role played in thyroid papillary thyroid carcinoma (PTC) remains unclear. Objective of the study is to determine whether c-erbB-2 overexpression correlates with the clinical course. METHODS: We have studied 32 PTC by a two-step immunocytochemical staining procedure for paraffin-embedded specimens (DAKO Hercep-Test). Semiquantitative evaluations were performed, based on the intensity of immunostaining and the percentage of tumor cells. RESULTS: 34% (11/32) of the PTC showed a membranous overexpression of the HER2/neu oncoprotein. Correlating the pathological and clinical data revealed that 81% (9/11) c-erbB-2 positive patients and only 33% (7/21) c-erbB-2 negative patients developed a tumor recurrence or a progression (p = 0.02 in Fisher's exact test). 3/11 c-erbB-2 positive patients died from PTC whereas all (21/21) c-erbB-2 negative patients are still alive (p = 0.03). CONCLUSIONS: Our results strongly suggest that c-erbB-2 oncoprotein overexpression is related to the clinical course of PTC.

Value of (124)I-PET/CT in staging of patients with differentiated thyroid cancer.

The aim of this study is to evaluate the clinical significance of (124)I positron emission tomography (PET) using a combined PET/CT tomograph in patients with differentiated thyroid carcinoma and to compare the PET/CT results with (131)I whole-body scintigraphy (WBS), dedicated PET and CT alone. Twelve thyroid cancer patients were referred for diagnostic workup and entered complete clinical evaluation, including histology, cytology, thyroglobulin level, ultrasonography, fluorine-18 fluorodeoxyglucose (FDG)-PET, FDG-PET/CT and CT. Lesion-based evaluation showed a lesion delectability of 56, 87 and 100% for CT, (124)I-PET, and combined (124)I-PET/CT imaging, respectively. Lesion delectability of (131)I-WBS was 83%. We conclude that (124)I-PET/CT imaging is a promising technique to improve treatment planning in thyroid cancer. It is particularly valuable in patients suffering from advanced differentiated thyroid cancer prior to radio-iodine therapy and in patients with suspected recurrence and potential metastatic disease.

Impact of disease activity on thyroid diseases in patients with acromegaly: basal evaluation and follow-up.

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.

FDG-PET/CT in re-staging of patients with lymphoma.

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.

[Hyperplasia of the thyroid gland]. / Hyperplasien der Schilddrüse.

Hyperplasia of the follicular epithelium (goitre) is the most common morphological change in the thyroid seen by the pathologist. The present paper deals with the aetiology, epidemiology and clinical features of thyroid hyperplasia and its differential diagnosis from thyroid adenoma. Neoplastic hyperplasia of the calcitonin-producing thyroid C cells gives rise to familial medullary carcinoma. The second part of the paper deals with the definition of neoplastic C cell hyperplasia and its discrimination from physiological C cell hyperplasia.