Optimal institutional Tg cut-off levels for diagnosis and prognosis should be defined using ROC analyses for each condition and time-point. Tg measurements 6 months after initial therapy during TSH stimulation had an excellent diagnostic value. Tg levels are independent prognostic indicators for disease-free remission and death. Using this strategy, high-risk patient groups can be selected based on Tg levels, in addition to conventionally used prognostic indicators.

Objectives: The microscopic distinction between benign and malignant thyroid lesions in clinical practice is still largely based on conventional histology. This study was performed to evaluate the diagnostic value of galectin-3 (Gal-3), Hector Battifora mesothelial-1 (HBME-1), cytokeratin (CK)-19, CBP P300-interacting transactivator with glutamic acid E-and aspartic acid D-rich C-terminal domain (CITED-1), fibronectin (FN)-1, peroxisome proliferator-activated receptor (PPAR)-g, and intracellular sodium/iodide symporter (iNIS) immunostaining in a large panel of thyroid neoplasms. Our study differed from earlier ones with regard to the identification of optimal semiquantitative cut-off levels using receiver operator curve (ROC) analysis and hierarchical cluster analysis. Methods: We used tissue arrays containing 177 thyroid tissues: 100 benign tissues (including normal thyroid, Graves disease, multinodular goiter, and follicular adenoma (FA)) and 77 thyroid carcinomas (including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, and follicular variant of PTC (FVPTC)). Antibody staining was scored semiquantitatively based on the ROC analyses and with hierarchical cluster analysis. Results: In general, we found overexpression of FN-1, CITED-1, Gal-3, CK-19, HBME-1, and iNIS in malignant thyroid lesions. Gal-3, FN-1, and iNIS had the highest accuracy in the differential diagnosis of follicular lesions. A panel of Gal-3, FN-1, and iNIS, identified by hierarchical cluster analysis, had a 98% accuracy to differentiate between FA and malignant thyroid lesions. In addition, HBME-1 was found to be useful in the differentiation between FA and FVPTC (accuracy 88%). Conclusion: We conclude that identifying optimal antibody panels with cluster analysis increases the diagnostic value in the differential diagnosis of thyroid neoplasms, the combination of FN-1, Gal-3, and iNIS having the best accuracy (98%). 158 375-384 European Journal of Endocrinology

Objective: Treatment options for metastases of differentiated thyroid carcinoma (DTC) are limited due to decreased uptake of radioiodide (I-131). Therefore, strategies to improve I-131 uptake are mandatory. It has been suggested that retinoids have beneficial effects on iodide uptake in vitro and in humans. However, to date, only studies with 13-cis-retinoic acid have been performed in humans. We therefore decided to study the effects of 6 weeks of treatment with the retinoid X receptor activator bexarotene on I-131 uptake in patients with metastatic DTC. Design: Open prospective intervention study. Methods: Twelve patients with metastases of DTC, with insufficient uptake of I-131, received 6 weeks of treatment with 300 mg bexarotene/day. Prior to, and after this intervention, I-131 uptake was measured by whole-body scintigraphy and single photon emission tomography (SPECT) 3 days after 185 MBq I-131. Diagnostic imaging was preceded by two consecutive injections of recombinant human TSH. Results: Bexarotene treatment induced I-131 uptake in metastases of 8 out of 11 patients (one patient died for reasons not related to the study). However, uptake was only discernable at SPECT and had incomplete matching with metastases as visualized by CT scanning. Conclusions: Bexarotene partially restores I-131 uptake in metastases of DTC. The clinical relevance of this observation may be limited due to the differential responses of the different metastases within each patient and the low intensity of I-131 uptake.European Journal of Endocrinology 154 525-531

Background: Although differential expression of retinoic acid receptor (RAR) subtypes between benign and malignant thyroid tissues has been described, their diagnostic value has not been reported. Aim: To investigate the diagnostic accuracy of RAR and retinoid X receptor (RXR) subtype protein expression for the differential diagnosis of thyroid neoplasms. Methods: We used a tissue array containing 93 benign thyroid tissues (normal thyroid, multinodular goiter, and follicular adenoma (FA)) and 77 thyroid carcinomas (papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, and follicular variant of PTC (FVPTC)). Immunostaining was done for RAR and RXR subtypes. Staining was analyzed semiquantitatively based on receiver operating curve analyses and using hierarchical cluster analysis. Results: We found increased expression of cytoplasmic (c) RARA, cRARG, cRXRB and decreased expression of nuclear (n) RARB, nRARG, and nRXRA in thyroid carcinomas compared with benign tissues. We found three proteins differently expressed between FA and FTC and five proteins differentially expressed between FA and FVPTC, with high diagnostic accuracies. Using cluster analysis, the combination of negative staining of membranous RXRB and positive staining for cRXRB had a high positive predictive value (98%) for malignant thyroid disease, whereas the combination of positive nRXRA and negative cRXRB staining had a high predictive value (91%) for benign thyroid lesions. Conclusion: We conclude that differences in RAR and RXR subtype protein expression may be valuable for the differential diagnosis of thyroid neoplasms. The results of this study and especially the value of cluster analysis have to be confirmed in subsequent studies.

Bexarotene therapy did not result in restoration of susceptibility to radioiodine therapy.