Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells

OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hürthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P < .05). A higher incidence of malignancy was found in males, but the data did not reach statistical significance (P = .0586). CONCLUSION: Most of the follicular neoplasms revealed by FNAC were benign lesions. Low echo density on ultrasonography and male sex carried a higher risk of malignancy.     

Comparison of intraoperative cytology with frozen sections in the diagnosis of thyroid lesions

We retrospectively studied the usefulness of intraoperative cytology (IOC) and frozen section (FS) in the rapid diagnosis of 68 thyroid lesions. In 14 cases of papillary thyroid carcinoma, IOC correctly diagnosed 13 cases, while FS correctly diagnosed 11 cases. There was no significant difference in sensitivities, and both methods had similar specificities. In 21 cases of colloid nodule, IOC was slightly more sensitive than FS; IOC correctly diagnosed 16 cases, while FS correctly diagnosed 15 cases. However, the specificity of IOC was only 71%, but was 98% for FS. Of 17 follicular adenomas, FS diagnosed 16 as follicular neoplasms and misdiagnosed only 1 as a colloid nodule. By contrast, IOC misdiagnosed 9 follicular adenomas as colloid nodules, most of which were macrofollicular variants with abundant colloid. Of 11 follicular carcinomas, FS diagnosed all as follicular neoplasms, while IOC misdiagnosed 3 as colloid nodules. While IOC is not as accurate as FS in the diagnosis of colloid nodules and follicular neoplasms, it is highly sensitive and specific in the diagnoses of papillary carcinoma and performance of the technique is rapid and easy. In an intraoperative setting, IOC is a useful adjunct to FS in screening thyroid nodules for the presence of papillary carcinoma.     

Two-dimensional electrophoretic analysis of membranous protein from human thyroid tissues and cancer cell lines

Thyroid neoplasm is the most commonly encountered neoplastic disorder in endocrine clinics. Thyroid scan, ultrasonography, and fine needle aspiration cytology (FNAC) are used as diagnostic tools to differentiate a malignant nodule from a benign lesion. There are certain limitations and pitfalls in FNAC, especially in the diagnosing of follicular tumors. The lack of characteristic findings or a specific tumor marker are the most common problems in the preoperative diagnosis of thyroid follicular carcinoma. Although serum thyroglobulin level has been used as a tumor marker for post-operative, well-differentiated thyroid cancer, the assay cannot be used for preoperative diagnosis of thyroid carcinoma. In this study, various thyroid tissues and cancer cell lines including CGTH W-1, CGTH W-3, RO 82 W-1, SW 579 cell lines were used for the investigation of tumor markers. Specific spots were identified in the area near the 60 kDa molecular mass protein and isoelectric point (pI) 5.9 of the CGTH W-1 cell line. These spots could not be found in the papillary or anaplastic thyroid cancer cell lines. Another spot with a molecular weight of about 9.8 kDa with a low pI of 4.8 was present in the CGTH W-1 and RO 82 W-1 cell lines. This spot appeared to be a tumor marker of follicular cancer cells. This spot could not be found in the papillary and anaplastic cancer cell lines and other benign thyroid tissues. Specific proteins that were identified in this study may be useful as tumor markers for follicular thyroid carcinoma.     

Clinical presentations and predictive variables of thyroid microcarcinoma with distant metastasis

BACKGROUND: Thyroid microcarcinoma is not an uncommon disorder. The purpose of this study is to analyze the clinical presentation and predictive factors for patients with thyroid microcarcinomas who have distant metastases. METHODS: We retrospectively reviewed and analyzed the clinical variables of 97 patients with thyroid microcarcinoma during the period from 1977 to 1995. The patients were divided into 2 groups representing patients with and without distant metastases. These data were analyzed by the Mann-Whitney U, chi 2 and Fisher's exact tests. RESULTS: Of the 97 patients with thyroid microcarcinomas, there were 6 (6.2%) cases (F/M = 5/1) with distant metastases. Among them, 4 cases were papillary carcinomas and 2 cases were follicular carcinomas. The parameters: age at diagnosis (P = 0.0137), one month postoperative serum thyroglobulin (Tg) level (P = 0.0215), cervical lymph node metastasis (P = 0.0097), and follicular cell type (P = 0.0079), were determined to be factors predictive for distant metastases by statistical analysis. There were no statistical differences between gender (P = 0.5781), postoperative 131I uptake (P = 0.1238), tumor size (P = 0.0571), preoperative thyroid function (P = 0.4425), fine-needle aspiration cytology (FNAC) (P = 0.9723), preoperative thyroid scan (P = 0.9765), and operative methods (P = 0.1060) between these two groups. CONCLUSIONS: Most thyroid microcarcinomas presented with relatively benign clinical courses, but patients with adverse predictive factors need more aggressive interventions to improve outcome.     

Solitary thyroid nodule in Khartoum

Ninety four patients with solitary and significantly dominant thyroid nodules were studied. Inadequate sampling was reported in 5 patients (5.9%). In the remaining 89 patients, 64 had simple goitre (72%), 12 follicular adenoma (13.5%), 12 were malignant nodules (6 follicular, 5 papillary and one anaplastic) (13.5%) and one patient had Hashimoto's thyroiditis. The incidence of malignancy in the clinically solitary nodules was 14% (10/70) compared to 10% (2/19) for the dominant nodules which increased to 16% (8/49) versus 10% (4/40) respectively after ultrasonography and histopathological confirmation of the nature of the gland. There is a low positive predictive value for follicular neoplasm with fine needle aspiration cytology (FNAC) (44%). This is due to the fact that reports of suspicious follicular pattern is agreed not to imply definite malignancy, however total lobectomy was done for those patients whereas terms like "not suspicious" and "highly suspicious" are considered to mean, benign and malignant respectively and in those latter groups the prediction was 100%. The study stresses the importance of FNAC techniques in reducing the surgical load with minimal false negative results, increasing the yield of carcinoma and projecting the importance of a significantly dominant nodule in endemic areas.     

Hyperthyroidism and carcinoma of the thyroid gland

The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a few tumors are suspected preoperatively with ultrasonography or fine needle aspiration or 131 I scan. In 408 patients who underwent surgery for hyperthyroidism in our Surgery Department from January 1967 through December 1994 the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.     

Clinical significance of clonality in thyroid nodules

BACKGROUND: Many different neoplastic and hyperplastic thyroid diseases present with clinically apparent thyroid nodules. Clonality analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell and thus provides objective information on the origin of the thyroid nodules. Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women. METHODS: DNA samples were obtained from 28 nodules in 21 women. All nodules and non-tumour thyroid tissues were fractioned selectively under a cryostat. Genomic DNA was isolated and digested with HhaI. PCR amplification of the HUMARA locus was performed using PCR mixtures containing [alpha-32P]2'-deoxycytidine 5'-triphosphate. The PCR products were analysed by denaturing gel electrophoresis. RESULTS: The HUMARA alleles were heterogeneous in 18 of 21 patients. Among the 23 nodules from 18 patients, all of the eight papillary thyroid carcinomas were monoclonal. Two solitary nodules from follicular adenomas were monoclonal. Of the 13 follicular nodules from nodular goitres, ten were polyclonal and three were monoclonal. The monoclonal follicular nodules were larger in size (3.5 versus 2.0 cm, P< 0.05) and had a tendency towards more cystic changes than polyclonal nodules. CONCLUSION: PCR-based clonality study of thyroid nodules may help to distinguish hyperplastic from neoplastic nodules.     

Expression of glutathione-peroxidase (GSH-PO) in the rat ventral prostate--effect of castration and administration of testosterone

This series retrospectively reviewed 3657 patients who received thyroid ultrasonography with fine-needle aspiration cytological (FNAC) examinations at Chang Gung Memorial Hospital during the period from January 1, 1993 to December 31, 1993. Thyroid ultrasonography studies were performed using a real-time ultrasonographic machine with a 10 MHz transducer. The aspirates were air dried and stained by the Romanowsky-based Liu method. Three hundred seventy-eight cases (10.3%) received surgical treatment after the ultrasonographic and FNAC examinations. Benign lesions were diagnosed in 269 patients. Thyroid malignancy was confirmed histopathologically in 109 cases including 76 papillary thyroid carcinomas, 17 follicular carcinomas, 5 medullary thyroid carcinomas, 3 anaplastic carcinomas, 3 Hürthle cell carcinomas, and 3 lymphomas. Another 2 cases were metastatic cancer to thyroid. The results demonstrated that 28.8% of the surgically treated patients had histopathologically proven malignancies. The incidence of thyroid malignancy was 2.98% in this study. The sensitivity of the cytological diagnosis was 79.80% and the specificity was 98.66%. The positive predictive value was 96.34%. Negative predictive value was 91.70%. The false negative index was 20.20%. The diagnostic accuracy was 92.89%. Thyroid ultrasonography with the FNAC can provide high specificity and sensitivity in differentiating malignant lesions from benign.     

Immunohistochemical analysis of p27/kip1 expression in thyroid carcinoma

Cyclin-dependent kinase inhibitors, including the protein product of the p27/kip1 gene, play an important role in cell-cycle regulation. Loss of p27 expression was reported in a number of neoplasms and shown to be an independent prognostic factor in colorectal, lung, and breast carcinoma By immunohistochemical analysis, we investigated p27/kip1 expression, using a polyclonal antibody, in a series of 87 benign and malignant thyroid neoplasms. We correlated its expression with the Ki-67 labeling index and other prognostic factors. All of the thyroid neoplasms examined exhibited significantly lower p27 expression than did normal thyroid tissue (P < .001). Poorly differentiated carcinomas had the lowest p27 staining frequency of all carcinomas examined. p27 staining frequency of the papillary carcinomas was significantly lower than that of the follicular carcinomas (P < .001). This difference could not be attributed solely to the inverse correlation between the staining patterns of p27 and Ki-67, which was reported for other neoplasms, because there was no significant difference between the Ki-67 labeling indices of these two groups. The follicular variant of papillary carcinoma had a significantly higher p27 staining frequency (P = .05) than did classical papillary carcinoma. We saw no significant difference in the p27 staining frequencies between minimally and widely invasive follicular carcinomas nor between localized and nonlocalized papillary carcinoma. In summary, the p27 immunostaining pattern of thyroid neoplasms is related to neoplastic transformation and varies according to tumor phenotype. It seems, however, to have limited routine diagnostic or prognostic significance in thyroid neoplasia.     

Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer

Fine-needle aspiration cytology (FNAC) is the most useful procedure for the evaluation of thyroid nodules. The requirement for repeated aspirations in the follow-up of benign nodular thyroid disease, however, is controversial. To determine the value of re-aspirations in benign nodular thyroid disease, we studied 457 fine-needle reaspirations performed on 216 patients (197 female, 19 male) aged 42.9+/-12 years with uninodular (n = 65) and multinodular (n = 151) thyroid disease. Two hundred fifty-seven of these were second, 137 were third, 46 were fourth, and 17 were fifth re-aspirations of the same nodule, performed in a mean follow-up time of 43.9+/-31 (3-156) months. FNAC results were benign in 407 (89%), insufficient for diagnosis in 31 (6.8%), suspicious in 16 (3.5%), and papillary carcinoma (PC) in 3 (0.7%). An initial benign diagnosis did not change after multiple aspirations in 213 (98.61%) of the cases. Three patients with initial aspirations read as benign had a diagnosis of PC from their second biopsies, (diagnosis confirmed at surgery). Re-examination of the initial FNAC revealed atypical features in 1 of the 3 patients. These 3 patients likely represent a false-negative result of the initial FNAC rather than benign nodular disease transformed to a malignant one during the follow-up period. In conclusion, a second aspiration of clinically suspicious nodules may correct a few initial false-negative results, but routine additional re-aspirations are not useful for clinically stable disease.     

A neural network that predicts psychiatric length of stay

One hundred and twelve bilateral thyroidectomies for solitary thyroid nodules with suspected malignancy were performed. The incidence of malignancy in the 112 primary nodules was 42%. Twenty-nine of the 112 contralateral lobes (26%) contained malignancy, which was unsuspected in 80%. Of these 29, 20 were foci of papillary cancer < or = 5 mm and 9 were larger papillary tumors or follicular carcinoma. We analyzed these 112 patients to determine whether there was a simple method to identify those patients at risk for contralateral, unsuspected malignancy. With use of the AMES clinical staging retrospectively, 70 of the 112 patients were classified as having low-stage disease. Fifty percent (35) had cancers on the primary side and 27% (19) on the contralateral side. Of these 19 contralateral cancers, 14 were papillary cancers < or = 5 mm, 4 were papillary cancer > 5 mm and one was a 1.5 cm follicular carcinoma, a similar distribution as in the whole group of 112. When the AMES analysis then excluded those thought to be at risk for multicentricity or papillary carcinoma and examined female patients only with nonpapillary frozen sections, nonpapillary aspiration cytological results, and no history of radiation exposure, no further reduction in the proportion of contralateral cancers (7 of 26, 27%) was found. Fifty-five of the 112 patients underwent preoperative ultrasound scans. In those cases in whom the contralateral lobe had no intraoperative palpable or preoperative sonographic mass, 5 of 20 still had contralateral cancers, but all were papillary < or = 5 mm.(ABSTRACT TRUNCATED AT 250 WORDS)     

c-Met expression of thyroid tissue with special reference to papillary carcinoma

It has become clear that papillary carcinomas of the thyroid often express the receptor for c-Met/hepatocyte growth factor (HGF) receptor, but little is known about the role of the HGF and c-Met system in the pathogenesis of thyroid carcinoma. In this study, the expression of c-Met/HGF receptor was evaluated in thyroid tissue by western blot and immunohistochemistry, and compared with the concentration of HGF. Clinicopathological characteristics were also compared. Fifteen of 20 papillary carcinomas (75%) showed c-Met bands of 145 kDa. No or only a low frequency of c-Met expression was detected in healthy thyroid tissue (0/5), thyroiditis or Basedow's disease (0/2), adenomatous goiters (0/8), follicular adenomas (1/9, 11%) and undifferentiated carcinomas (0/2). These results were confirmed by immunohistochemistry, but a relatively higher frequency of c-Met expression was detected in adenomatous goiters (25%), follicular adenoma (44%) and papillary carcinoma (100%) using formalin-fixed and paraffin-embedded materials. A strong immunoreaction for c-Met was observed in the tumor cytoplasm of papillary carcinomas among the fibrous tissues situated at the periphery of the tumor. The densitometrically measured expression of c-Met had no relation to tumor stage in papillary carcinoma, but did correlate to the concentration of HGF in papillary carcinomas. In conclusion, in thyroid lesions, c-Met was highly expressed specifically in the cytoplasm of papillary carcinomas. c-Met expression was not related to the aggressiveness of the tumor but was related to the concentration of HGF, which was probably derived from the stroma. Also, the c-Met system might play a role in the pathogenesis of papillary carcinoma of the thyroid.     

Post-Chernobyl thyroid carcinoma in Belarus children and adolescents: comparison with naturally occurring thyroid carcinoma in Italy and France

After the Chernobyl nuclear accident (April 26, 1986), childhood thyroid carcinoma had a great increase in Belarus and Ukraine, as a consequence of the exposure to iodine radioactive fallout. The epidemiological and clinical features of the disease were studied in 472 patients less than 21 yr old at diagnosis, with differentiated thyroid carcinoma, representing 97.7% of all thyroid carcinomas diagnosed in Belarus between May, 1986, and December, 1995. The results were compared with those of 369 subjects of the same age group, with naturally occurring thyroid carcinoma, observed in Italy and France. Between 1986 and 1989, the number of thyroid cancer cases per year ranged from 3-8 and increased to 31 in 1990, to 66 in 1991, to 72 in 1992, to 93 in 1993, to 96 in 1994, and to 90 in 1995. The age at diagnosis was 14 yr or less in 78.8% (children group) and more than 14, but less than 21, yr in the remaining subjects (adolescents group). Mean (+/- SD) age at the time of the accident was 4.4 +/- 3.4 yr (3.2 +/- 2.3 in children and 8.9 +/- 2.7 in adolescents), the majority of the patients (62.9%) being 5 yr old or less. The time interval between the accident and the diagnosis (latency period) decreased progressively from 7.5 +/- 1.6 yr in children 0-2 yr old at the time of the accident to 6.0 +/- 1.6 yr in those 9-11 yr old. Since 1993, the yearly distribution of new cases showed a decrease in the subjects 9 yr old or more at the time of the accident but not in those 5 yr old or less. This could not be accounted for by a shift of exposed subjects to an age group at diagnosis not included in this study, because only subjects less than 12 yr of age at the time of the accident were considered in this analysis. Mean age at diagnosis in Belarus patients was 11.3 +/- 3.1 yr (10.1 +/- 2.3 in children and 15.7 +/- 1.4 in adolescents), whereas, among patients with naturally-occurring thyroid carcinomas from Italy and France, the majority of cases were diagnosed after 14 yr of age (mean age at diagnosis: 14.6 +/- 4.2 yr). The female-to-male ratio was significantly higher in Italy and France (2.5/1), compared with the ratio of patients from Belarus (1.6/1). Most of the tumors were papillary in both series, but a relatively high proportion of follicular carcinomas (P = 0.0001) was found in Italy/France (15.2%), as opposed to 5.3% in Belarus. Extrathyroidal extension and lymph node metastases were more frequent in Belarus (49.1%, P = 0.0001; and 64.6%, P = 0.002, respectively) with respect to Italy/France (24.9% and 53.9%, respectively). Thyroid lymphocytic infiltration and circulating antithyroperoxidase antibody were more frequent in Belarus patients. Our analysis of Belarus thyroid cancer patients less than 21 yr old showed that the post-Chernobyl increase in thyroid carcinomas involved both children and, to a much lesser extent, adolescents. Subjects 5 yr old or less at the time of the accident accounted for the majority of the patients. No evidence of a decrease in the number of new cases was observed in this age group, as opposed to older subjects. These data support the concept that subjects who were younger at the time of radiation exposure had, and continue to have, a greater risk of developing thyroid carcinoma and strongly suggest that this age group should be carefully monitored in the future. When compared with naturally occurring thyroid carcinoma of the same age group observed in Italy and France, the post-Chernobyl Belarus thyroid carcinomas affected younger subjects, were less influenced by gender, were virtually always papillary, had a greater aggressiveness at presentation, and were more frequently associated with thyroid autoimmunity.     

Telomerase activity in the differential diagnosis of papillary carcinoma of the thyroid

BACKGROUND: Although fine-needle aspiration (FNA) is 90% sensitive in the detection of papillary carcinoma (PC) of the thyroid, its specificity has been reported as low as 52%. Consequently, patients who have an FNA suspicious for PC may undergo operation for a benign process. The ribonucleoprotein telomerase has been noted to be activated in a wide variety of carcinomas. We examined 30 PCs for telomerase activity to determine whether this would be a useful adjunct to FNA in the diagnosis of lesions suspicious for PC. METHODS: Standard telomere repeat amplification protocol assays were performed on fresh frozen tissue samples from 30 PCs, 3 benign nodules, and 10 normal thyroids. RESULTS: Telomerase activity was documented in 20 of 30 (67%) of the PCs, 0 of 3 benign nodules, and 0 of 10 normal thyroids. In all, 11 of the 20 PCs had FNA cytology that was nondiagnostic of PC, and 2 of the benign nodules had FNA that was suspicious for PC. CONCLUSIONS: The telomerase assay appears useful in the distinction of benign from malignant thyroid lesions that have FNA suspicious for but not diagnostic of PC. On the basis of these findings, a prospective trial examining telomerase activity in FNAs suspicious for thyroid cancer has been initiated.     

Significance of nondiagnostic fine-needle aspiration of the thyroid

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been shown to be rapid and cost effective in the evaluation of thyroid nodules. The significance of nondiagnostic (unsatisfactory) FNAB is uncertain, however. METHODS: We reviewed 345 consecutive thyroid FNABs and identified 59 patients with initially unsatisfactory specimens. These patients had follow-up to determine whether their thyroid nodules proved to be malignant. RESULTS: Three patients (5.1%) were found to have organ-confined papillary carcinoma of the thyroid, the largest tumor mass measuring 1.2 cm. Six patients (10.2%) had benign adenomas. CONCLUSIONS: In most cases of initially nondiagnostic FNAB of a thyroid nodule, neoplasia is not found subsequently. A minority of cases may still harbor malignancy. None of our patients in whom repeated FNA was either nondiagnostic or suggestive of benign disease were ultimately found to have a malignancy.     

Redifferentiation therapy-induced radioiodine uptake in thyroid cancer

Due to a dedifferentiation of tumor cells, some thyroid carcinomas lose their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment. Retinoic acid (RA) is known to induce redifferentiation in various kinds of tumors and has been used recently in thyroid cancer. METHODS: Twelve patients (9 women, 3 men) with 6 papillary, 4 follicular and 2 mixed-cell type tumors (including 4 Hurthle cell carcinomas) were treated orally with RA (dose: 1.18 +/- 0.37 mg/kg body weight) for at least 2 mo before RI therapy. None of the patients could be treated with any other modality (RI, surgery, external radiation) when RA administration was started. Initially, clinically important tumor sites did not take up significant amounts of RI. Changes of RI uptake and thyroglobulin (Tg) serum values were determined. Glucose metabolism was followed with fluorodeoxyglucose (FDG) PET imaging in 10 patients before and in 5 patients after RA treatment. RESULTS: In 2 patients, a significant RI uptake was induced by RA, and in another 3 patients a faint RI uptake was achieved (responder group). In 7 patients, no change of RI uptake was observed (nonresponder group). Median Tg was increased from 105-840 microg/liter during RA therapy in the responder group, which was significantly higher than the nonresponder group (173-134 microg/liter). FDG PET was positive in all 10 patients before RA therapy. PET showed variable patterns of changes (increase/decrease/disappearance) in glucose consumption related to RA response. CONCLUSION: RA can induce RI uptake in some patients with RI negative thyroid carcinoma tumor sites. Response to RA is associated with a significantly higher increase of Tg, suggesting that a restoration of Tg synthesis can be addressed as a redifferentiation parameter in these patients.