High Serum Thyroglobulin Research Articles

Diagnostic value of 18F-FDG PET/CT in patients with TENIS syndrome: correlation with thyroglobulin levels

The aim of the study was to disclose the place of (18)F-FDG PET/CT to predict recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Seventy-one patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels underwent PET/CT. They were followed up for 6-50 months (median 23) for the occurence of recurrent disease as detected by either clinical findings, other imaging modalities or histopathological examination. The place of PET/CT findings at baseline to predict the presence of recurrent disease was evaluated. Correlation between PET/CT findings and Tg levels was examined and a threshold for Tg level above which the predictive value of PET/CT was highest was determined. PET/CT was positive for recurrent disease in 38 (53.5%) patients. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of PET/CT to predict the occurence of recurrent disease at follow-up were 68.8, 78.3, 86.8, 54.5 and 71.9%, respectively. The sensitivity, accuracy and PPV of PET/CT increased with increasing Tg levels. The highest diagnostic accuracy of PET/CT, with a sensitivity of 76.2% and a specificity of 100% to detect recurrent disease appeared to be at a Tg level greater than 29 ng/mL. Our findings suggest that (18)F-FDG-PET/CT is a valuable tool to predict the occurence of recurrent disease in patients with DTC, negative WBS and elevated Tg levels. PET/CT positivity has been shown to be strongly and positively correlated with Tg levels in this patient subset.

Axillary Lymph Node Metastasis of Papillary Thyroid Carcinoma Detected by FDG PET/CT in a Thyroglobulin-Positive Patient With Negative Whole-Body 131I Scan

Axillary metastasis is not a common finding in papillary carcinoma. 18F-FDG can detect foci of metastasis in patients with negative 131I scan. We report a case of a 64-year-old man who had undergone thyroidectomy and 131I ablation due to classic type of papillary carcinoma 14 years ago. Follow-up examination revealed high serum thyroglobulin and negative whole body 131I scan. 18F-FDG PET/CT showed focally increased uptake in right axillary as well as supraclavicular and bilateral cervical lymph nodes. Histopathological examination of the surgically removed lymph nodes confirmed the metastasis of papillary thyroid carcinoma.

Evaluation of cytologically benign solitary thyroid nodules by ultrasonography: A retrospective analysis of 1877 cases

The purpose of this study is to evaluate the role of ultrasonography (US) in the management of thyroid nodules when the cytology is benign tumor on fine needle aspiration biopsy (FNAB). Between 2006 and 2011, we investigated 13,972 patients who had solitary thyroid nodule with cytological findings of benign. Surgery was performed according to our criteria for surgical indication. Of these patients, 1877 (13%) patients who underwent surgery were enrolled in this study. We compared the results of clinical findings including US classification and final histopathological diagnosis. One hundred seven (6%) after surgery were diagnosed as malignancy pathologically. Large nodule or high serum thyroglobulin level were not associated with an increased risk of malignancy. Ultrasonographic evaluation as malignancy was directly linked to pathological diagnosis as thyroid carcinoma (p<0.001). US may help to play a role in deciding whether surgical treatment is necessary for cytologically benign thyroid nodules.

18F-FDG PET/CT changes therapy management in high-risk DTC after first radioiodine therapy

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.

Detection of Subcentimeter Metastatic Cervical Lymph Node by 18F-FDG PET/CT in Patients With Well-Differentiated Thyroid Carcinoma and High Serum Thyroglobulin But Negative 131I Whole-Body Scan

This study aimed to evaluate the diagnostic value of 18F-FDG PET/CT and identify the best parameter to detect subcentimeter cervical nodal metastasis in patients with a well-differentiated thyroid carcinoma (WDTC), elevated serum thyroglobulin (Tg) levels, but negative findings in the 131I whole-body scan (WBS). We prospectively studied 30 consecutive patients with WDTC after standard surgery and radioiodine treatment. All patients had serum Tg greater than 10 ng/mL during thyroid hormone withdrawal but negative findings in the therapeutic 131I WBS. One whole-body CT scan and serial whole-body and neck PET scans were performed between 10 and 170 minutes after 18F-FDG injection. Parameters studied were SUVmax, percent change in SUVmax, SUV ratios of lesions to reference organs, and their percent change. Result in the PET/CT scan was correlated with histopathology and follow-up information. Patient-based and lesion-based (subcentimeter cervical lymph nodes) analyses were performed. Outcome of Tg level after lymph node resection was also analyzed. The overall sensitivity, specificity, accuracy, and positive and negative predictive values were 100%, 78%, 93%, 91%, and 100%, respectively. In lesion-based analysis, the differential SUVmax between 2 time points did not provide higher sensitivity than the individual SUVmax at the 60th or 90th minute. A combined SUVmax at the 90th minute greater than 2.75 and a percent change of SUVmax between the 60th and 90th minute greater than -1.1% provides the best diagnostic value with sensitivity, specificity, accuracy, and positive and negative predictive values of 81%, 90%, 83%, 97%, and 56%, respectively. After surgery, patients with completely resected PET-positive nodes without distant metastasis showed reduction of suppressed Tg to less than 2 ng/mL. Combined SUVmax at the 90th minute and the percent change of SUVmax between the 60th and 90th minute provides the best diagnostic value to differentiate benign from malignant conditions in subcentimeter lymph nodes.

The comparison of 131I whole-body scans on the third and tenth day after 131I therapy in patients with well-differentiated thyroid cancer: preliminary report

The purpose of the present study was to evaluate the clinical usefulness of the delayed post-therapeutic (131)I scan in patients with well-differentiated thyroid cancer by comparing the early scanned images with the delayed images. A total of 81 patients (female:male=67:14; age 52±13years) with well-differentiated thyroid cancer who underwent scans the third and tenth day after (131)I treatment were included in this study. The therapeutic dose ranged from 3.7GBq (100mCi) to 7.4GBq (200mCi). The early and delayed scan images were visually analyzed and the thyroid remnant-to-background uptake ratio (RBR) and the lesion-to-background uptake ratio (LBR) of metastatic lesions were calculated. Of the 81 patients, 5 lesions (2 lung lesions, 2 cervical lymph node lesions, and one thyroid remnant) in 4 patients (5%) were additionally found on the delayed scans, which were not identified on the early scans. Of 8 patients with high serum thyroglobulin (Tg) and negative finding on the early scan, the delayed scan identified additional lesions in 3 patients (38%). Visual analysis scores significantly decreased for both thyroid remnants and metastatic lesions on the delayed scan (p<0.001 for all). Diffuse hepatic uptake was visualized in 86% of all patients on the delayed scan, while only 6% of the patients on the early scan (p<0.001). The RBRs of both scans were compared in 59 patients, and the LBRs were compared in 8 patients with 23 lesions. The mean RBR and LBR on the delayed scan (8.0±7.6 and 5.4±5.2, respectively) were significantly lower than those on the early scan (12.0±10.8 and 10.8±7.6, respectively; p=0.02 and p=0.001, respectively). The (131)I-avid lesions on the early scan were more easily detected by visual analysis and had higher uptake ratios than those on the delayed scan. However, for patients with high serum Tg and negative finding on the early scan, the delayed scan was helpful in identifying additional (131)I-avid lesions.

Role of ultrasonography in patients with cytologically follicular thyroid tumor

The purpose of this study is to evaluate the role of ultrasonography (US) in the management of thyroid nodules when the cytology is indeterminate as follicular tumor on fine needle aspiration biopsy (FNAB). In 2006, 6586 patients with thyroid nodules, which were detected on US underwent FNAB in our department. Of these patients, we extracted 438 patients (6.7%) whose nodules were cytologically diagnosed as indeterminate. Of them, 227 patients were diagnosed as follicular tumor were enrolled in this study. Surgery was performed according to our criteria for surgical indication. We compared the results of clinical findings including US classification and final histopathological diagnosis. One hundred thirty-seven of 227 underwent surgical treatment. Thirty-three (24%) were diagnosed as malignancy pathologically. Large nodule or high serum thyroglobulin level were not associated with an increased risk of malignancy. Ultrasonographic evaluation as malignancy was directly linked to pathological diagnosis as thyroid carcinoma (p<0.0001). US plays a crucial role in deciding whether surgical treatment is necessary for cytologically indeterminate thyroid nodules as follicular tumor.

Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients affected by differentiated thyroid carcinoma, high thyroglobulin level, and negative 131I scan: review of the literature

Differentiated thyroid carcinoma (DTC) is a slow-growing tumor that represents 1% of all malignant tumors and is the most frequent endocrine cancer. ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) imaging is an increasingly important imaging tool in oncology and is still under investigation in numerous studies looking into its efficacy and cost-effectiveness. Despite the fact that ¹⁸F-FDG-PET/CT has been shown to be a powerful and accurate diagnostic tool in patients affected by DTC with high serum thyroglobulin (Tg) levels and negative radioiodine (¹³¹I) total body scan, its definitive role is not completely clear, in particular regarding the role of thyroid stimulating hormone (TSH) and Tg value "cutoff" over which is better to perform the study. In this review, these issues are analyzed to clarify controversial aspects and identify established cornerstones. In particular, the literature analysis suggests that levothyroxine withdrawal is preferable in cases of relatively low Tg levels (<10 ng/ml) and good clinical compliance to hypothyroidism. Moreover, recombinant thyrotropin stimulating hormone (rTSH) could be a preferable alternative in patients clinically unable to tolerate therapy withdrawal. A Tg cutoff level over which to perform the study seems to be 10 ng/ml, a reasonable value maintaining high accuracy in terms of a good compromise between sensitivity and specificity.

Ultrasound-guided fine-needle aspiration of thyroid nodules: stratification of malignancy risk using follicular proliferation grading, clinical and ultrasonographic features

To evaluate the diagnostic value of fine-needle aspiration (FNA) cytology and the additive contribution brought by clinical and ultrasound (US) features. Cytological and histological diagnoses were compared in a series of 924 patients who underwent US-guided FNA before surgery. We additionally developed a grading system for follicular proliferation (FP) FNA diagnosis, and investigated its impact on the malignancy risk as well as the additive contribution of clinical and US features by means of decision tree analysis. Excluding FP cases (n=395), our data demonstrated that strictly benign or malignant FNA diagnoses exhibit great concordance with benign or malignant histological diagnoses (97.8% accuracy). Our grading system that was applied to the 395 FP cases revealed that grades 1, 2 and 3 were associated with a 7.7, 17.7 and 45.7% incidence of malignancy respectively. Decision tree analysis resulted in a classification model which involved FP grade, patient's age, serum thyroglobulin level, nodule size and nodule uniqueness. This model identified a subgroup of patients with grade 1 FP nodules who were older than 50 years, and who had a higher risk of malignancy (17.9%). In addition, high serum thyroglobulin levels were associated with a very high malignancy risk (75.0%) for patients with grade 3 FP nodules. Finally, among grade 2 FP patients, unique and large nodules were associated with a high malignancy risk of 36.1%. The integration of FP grade, clinical and US features allows the stratification of patients with FP cytology according to their risk of malignancy.

Does Recombinant Human Thyrotropin-Stimulated Positron Emission Tomography with [18F]Fluoro-2-Deoxy-d-Glucose Improve Detection of Recurrence of Well-Differentiated Thyroid Carcinoma in Patients with Low Serum Thyroglobulin?

Thyrotropin (TSH) stimulates thyrocyte metabolism, glucose transport, and glycolysis. The interest in using recombinant human TSH (rhTSH) stimulation of fluoro-2-deoxy-D-glucose (FDG) with positron emission tomography (PET) has been shown, but mainly for patients with high serum thyroglobulin (Tg) concentration. We evaluated the use of rhTSH-stimulated PET-FDG in patients with low serum Tg concentration. Sixty-one PET/computed tomography (CT)-FDG (Biograph Sensation 16; Siemens Medical Solutions, Knoxville, TN) were performed in 44 patients (28 women and 16 men; 51 +/- 16 years) with positive Tg levels, negative or no contributive iodine-131 whole-body scintigraphy results, and no contributive morphological imaging results (ultrasound, magnetic resonance imaging, and CT). Thirty-eight patients had papillary carcinoma and six had follicular thyroid carcinoma. All patients had previously undergone total thyroidectomy and postoperative iodine ablation of thyroid bed remnant tissue. The rhTSH-stimulated PET/CT-FDG (5 MBq/kg) was performed after two 0.9 mg intramuscular doses of rhTSH (Thyrogen; Genzyme) which were administered 48 and 24 hours before imaging, while patients continued levothyroxine (LT(4)). Blood sampling was performed immediately before FDG injection for measurement of serum TSH and Tg concentrations (TSH(1) and Tg(1)) and after 48 hours (TSH(2) and Tg(2)). PET/CT-FDG findings were compared with the Tg: (i) at the initial iodine treatment during T(4) withdrawal (Tg(ini)), (ii) under T(4) (Tg(T4)) within 3 months before the PET/CT-FDG, (iii) with Tg(1), and (iv) with Tg(2). PET/CT-FDG findings were correlated with the findings of histology, iodine-131 whole-body scintigraphy, morphological imaging, or clinical follow-up. The mean Tg(ini) was 785 +/- 2707 microg/L for a TSH of 73 +/- 64 mU/L. The mean Tg(T4) was 7 +/- 15 microg/L (T(4) = 195 +/- 59 microg/day; mean TSH of 0.24 +/- 0.57 mU/L). Among the 44 patients, PET/CT-FDG findings were positive in 20 and negative in 24. Among the 61 PET/CT-FDG, 25 PET/CT-FDG were positive (41%). Among the 25 positive PET, the Tg(T4) values were less than 10 microg/L for 19, including 9 true-positive patients (20% of the 44 patients). There was no difference of PET/CT-FDG results (positive vs. negative) as related to the serum Tg concentrations (p = 0.99 for Tg(ini), p = 0.95 for Tg(T4), p = 0.07 for Tg(1), and p = 0.42 for Tg(2)). No relation was observed with PET/CT-FDG results and initial tumor size (p = 0.52) or node metastasis (p = 0.14). In the diagnosis of recurrent disease in patients with differentiated thyroid carcinoma and low Tg level, the sensitivity of rhTSH-stimulated PET/CT-FDG seems to be low and no correlation was observed between PET/CT-FDG findings and Tg level. However, positive PET-FDG results have been found in 9/44 (20%) patients with serum Tg levels lower than 10 microg/L. Therefore, this series shows that a cutoff value of 10 microg/L for the Tg under T(4) is probably not the best criteria to select patient candidates for PET/CT-FDG examination to detect the recurrence of differentiated thyroid carcinoma.

Is there any venous gradient in serum thyroglobulin levels in patients with differentiated thyroid cancer?

Some patients with differentiated thyroid cancer (DTC) have high serum thyroglobulin (Tg) levels although no evidence of disease can be detected on radioiodine scanning or other imaging methods. The aim of this study is to determine whether a gradient exists between the Tg levels of venous samples adjacent to primary tumour and systemic circulation. Twenty-six patients underwent thyroidectomy and/or lymph node dissection for primary and recurrent DTC. To detect Tg levels, blood samples were concurrently collected via venipuncture from the internal jugular vein adjacent to the tumor and ipsilateral antecubital vein. Serum Tg level was measured by a chemiluminescence assay. Tg levels were significantly higher in the adjacent internal jugular vein compared to the ipsilateral antecubital vein (p=0.001). The ratio of mean Tg values was higher 2.4-fold in the internal jugular vein than antecubital vein (median Tg ratio: 2.0:1; range, 0.7-29.6). Documentation of a venous gradient in Tg levels in patients with DTC is a new investigational topic. According to the results of this prospective study, venous sampling for Tg may be a useful tool to localize recurrent or perhaps persistent DTC in the neck for patients who have no detectable disease on radioiodine scans or other imaging studies.

Pacientes tratados por carcinoma diferenciado de tiroides con rastreos de 131I negativos y niveles de tiroglobulina elevada. Una evolución posible

Objective To verify the existence of patients with treated differentiated thyroid cancer (DTC) with negative 131I whole-body scanning (WBS) and high serum thyroglobulin (Tg) in the follow-up who evolve towards normalization without other therapy interventions. Material and methods Retrospective revision of the periodic examinations established in the protocol for patients with DTC, analyzing the levels of Tg found with IRMA annually in those with hormonal treatment and every 1-5 years in absence of previous hormonal treatment to WBS. Minimum surveillance of 2 years. Those who had elevated levels of Tg and WBS and other negative imaging tests in their course were selected. The characteristics of the patients selected were analysed in those whose Tg levels evolved to normalization without specific medical or surgical treatment (Group I) and those who did not reach normalization of Tg (Group II). Results A total of 130 patients (17.93 %) with high levels of Tg and negative WBS were detected. Group I: 31 patients (4.28 %), 11 men and 20 women; average age at the moment of the diagnosis of 33.4 years (rank: 5-60); average surveillance: 12.4 years (± 7.4). Histology: 27 papillary and 4 follicular carcinoma. Average ablation dose: 3.260 GBq (88,1 mCi); average total I 131 dose: 6.850 GBq (185.13 mCi). Tg normalization average time: 8.2 years. Group II: 99 patients (13.65 %), 27 men and 72 women. Average age of 40.4 years (rank: 7-76). Average surveillance: 9.8 years. Histology: 86 papillary and 13 follicular carcinoma. Average ablation dose: 3.266 GBq (88.28 mCi); average total 131I dose: 9.363 GBq (253,06 mCi). Two of the patients in group I had negative PET-FDG. There were 13 patients in whom progressive reduction of the levels of thyroglobulin without reaching normalization with negative PET-FDG was detected. Conclusions In patients with radiated DTC, deferred normalization of the levels of the serum thyroglobulin is possible. Empirical treatments cannot be considered the only factor that contributes to this result, which can occur without the administration of high-doses of 131I.

Patients treated for differentiated thyroid cancer with negative 131I whole-body scanning and elevated thyroglobulin levels. A possible course

Objective To verify the existence of patients with treated differentiated thyroid cancer (DTC) with negative 131I whole-body scanning (WBS) and high serum thyroglobulin (Tg) in the follow-up who evolve towards normalization without other therapy interventions. Material and methods Retrospective revision of the periodic examinations established in the protocol for patients with DTC, analyzing the levels of Tg found with IRMA annually in those with hormonal treatment and every 1-5 years in absence of previous hormonal treatment to WBS. Minimum surveillance of 2 years. Those who had elevated levels of Tg and WBS and other negative imaging tests in their course were selected. The characteristics of the patients selected were analysed in those whose Tg levels evolved to normalization without specific medical or surgical treatment (Group I) and those who did not reach normalization of Tg (Group II). Results A total of 130 patients (17.93 %) with high levels of Tg and negative WBS were detected. Group I: 31 patients (4.28 %), 11 men and 20 women; average age at the moment of the diagnosis of 33.4 years (rank: 5-60); average surveillance: 12.4 years (±7.4). Histology: 27 papillary and 4 follicular carcinoma. Average ablation dose: 32.60 GBq (88.1 mCi); average total 131I dose: 68.50 GBq (185.13 mCi). Tg normalization average time: 8.2 years. Group II: 99 patients (13.65 %), 27 men and 72 women. Average age of 40.4 years (rank: 7-76). Average surveillance: 9.8 years. Histology: 86 papillary and 13 follicular carcinoma. Average ablation dose: 32.66 GBq (88.28 mCi); average total 131I dose: 93.63 GBq (253.06 mCi). Two of the patients in group I had negative 18F fluoro-desoxyglucose (FDG-PET). There were 13 patients in whom progressive reduction of the levels of Tg without reaching normalization with negative FDG-PET was detected. Conclusions In patients with radiated DTC, deferred normalization of the levels of the serum Tg is possible. Empirical treatments cannot be considered the only factor that contributes to this result, which can occur without the administration of high-doses of 131I.

Iodine-123 as a diagnostic imaging agent in differentiated thyroid carcinoma: a comparison with iodine-131 post-treatment scanning and serum thyroglobulin measurement

Using 123I for diagnostic purposes avoids the risk of stunning for subsequent radioiodine treatment and affords an excellent image quality. In this study we assessed the role of 123I in comparison with 131I post-treatment imaging in patients with thyroid cancer. We compared a total of 292 123I scans with their corresponding post-treatment 131I images. Patients received a therapeutic dose of 131I following diagnostic scanning with 50-111 MBq of 123I. All patients were in a hypothyroid state (>30 microIU/l) before radioiodine administration for either diagnostic or therapeutic purposes. In 228 out of 263 patients with a positive diagnostic scan, 123I whole-body scan findings were concordant with those of corresponding post-treatment 131I images (concordance rate 87%). However, there were 44 additional foci of abnormal uptake on post-treatment 131I scans in 22 discordant cases with no impact on therapeutic management of the patients. In 13 patients, there was at least one new site on post-treatment images that had been missed on pretreatment 123I images. Twenty-nine patients with a negative diagnostic scan were treated with 131I owing to a high serum thyroglobulin level (range 11.3-480 ng/ml). Radioiodine uptake sites were seen in eight post-treatment scans. In 21 pairs of whole-body scans, both the pre- and the post-treatment scan were negative (concordance rate 72.4%). 123I scanning is comparable to high-dose 131I post-treatment imaging in thyroid carcinoma patients, and 123I offers excellent image quality as a diagnostic agent. It avoids disadvantages such as stunning before treatment and delivery of a high radiation dose to patients.

Association of SLC26A4 muations with clinical features and thyroid function in deaf infants with enlarged vestibular aqueduct

Pendred syndrome and non-syndromic recessive deafness associated with enlarged vestibular aqueduct (NSRD with EVA) are caused by mutations in the SLC26A4 (PDS) gene. Unlike NSRD with EVA, Pendred syndrome is characterized by goiter, which may be present after early adulthood. However, the clinical diagnosis of these two disorders is difficult in deaf children. Expression of the SLC26A4 gene may be responsible for iodide transport in the thyroid as well as for formation and function of the inner ear. Here, we analyzed the SLC26A4 gene and performed thyroid function tests (FT3, FT4, TSH, and Thyroglobulin) on six congenitally deaf infants (mean age 2.7 years) with EVA. Mutation of the SLC26A4 gene was identified in five patients: four were compound heterozygous (H723R/919-2A>G, H723R/IVS15+5G>A, H723R/R581S, IVS7-2A>G/IVS8+1G>A), the fifth had a frameshift mutation (322delC). All the patients demonstrated an elevation of serum thyroglobulin level. FT3 level was elevated in four of the five patients. The patient who did not have a detectable gene mutation showed normal thyroid function. We conclude that the mutations in the SLC26A4 gene identified here are highly associated with high serum thyroglobulin levels in congenital and deafness infants. These mutations may be of value for the diagnosis of Pendred syndrome and NSRD with EVA.

Mutations in the SLC26A4 (pendrin) gene in patients with sensorineural deafness and enlarged vestibular aqueduct.

Pendred syndrome and the enlarged vestibular aqueduct (EVA) are considered phenotypic variations of the same entity due to mutations in the SLC26A4 (pendrin) gene. Pendred syndrome consists in sensorineural deafness, goiter and impaired thyroid hormone synthesis while in EVA thyroid function seems to be preserved. The aim of this study was to evaluate thyroid function and morphology and to look for mutations in the SLC26A4 gene in patients presented with EVA. Among 57 consecutive patients with sensorineural deafness 15 with EVA, as assessed by magnetic resonance imaging (MRI), were identified and studied. A complete evaluation of thyroid function including thyroid echography and perchlorate discharge test was carried out in all patients with EVA; all exons of the SLC26A4 gene were amplified from peripheral leukocytes and directly sequenced, using specific intronic primers. Out of 15 patients with EVA, goiter was present in 8 (53%), hypothyroidism in 7 (47%), increased serum thyroglobulin levels in 8 (53%) and a positive perchlorate discharge test in 10 (67%). Nine alleles of the SLC26A4 gene were mutated: 2 novel mutations (L465W and G497R) and 4 already known mutations (T410M, R409H, T505N and IVS1001+1G>A) were found. Four subjects were compound heterozygous and 1 heterozygous (G497R/wt). All patients harbouring mutations in the SLC26A4 gene had goiter and a positive perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid. The remaining 10 patients had no mutations in the SLC26A4 gene: 4 of them were hypothyroid, 2 with goiter and positive perchlorate discharge test, 2 without goiter and with negative perchlorate discharge test. Two patients without mutations were euthyroid with positive perchlorate discharge test. Patients with mutations in the SLC26A4 gene had larger thyroid volume (p<0.002), higher serum thyroglobulin (Tg) levels (p<0.002) and greater radioiodine discharge after perchlorate (p=0.09) than patients without mutations. The results of the present study lend support to the concept that all patients with mutated SLC26A4 gene have abnormalities of thyroid function tests.

18F]Fluorodeoxyglucose Triple-Head Coincident Imaging as an Adjunct to 131I Scanning for Follow-Up of Papillary Thyroid Carcinoma

To evaluate the feasibility of using [(18)F]fluorodeoxyglucose ((18)FDG) triple-head coincidence imaging as a potential cost-effective alternative to positron emission tomography in the setting of suspected recurrence of papillary thyroid carcinoma. We retrospectively studied 10 patients with suspected recurrence of papillary carcinoma of the thyroid, who underwent (18)FDG coincidence imaging,(131)I scanning, and a reference anatomic scan (computed tomography, magnetic resonance imaging, or both) within 1 year in most cases. The (131)I scan detected the recurrence in five patients (62.5%) and failed to reveal recurrent cancer in three patients (37.5%); in contrast,(18)FDG imaging detected the recurrence in eight patients (100%) and was true negative in two patients in whom the scans were performed more than 1 year after effective therapy for the recurrence. The sensitivity of detection was unrelated to lesion size. The (18)FDG imaging results led to additional radiotherapy in all (131)I-negative patients, two of whom had high thyroglobulin levels and one of whom had a low thyroglobulin concentration but the presence of antithy-roglobulin antibodies. We conclude that (18)FDG triple-head coincidence imaging is useful for routine management of patients with thyroid cancer who have no abnormalities detected on (131)I scans but have high serum thyroglobulin levels. This technique, however, may not be as sensitive as a dedicated positron emission tomographic device, particularly for the assessment of small tumors.

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the planning of therapy and follow-up of patients with differentiated thyroid carcinoma after surgery.

The aim of this study was to investigate the possible role of technetium-99m methoxyisobutylisonitrile (MIBI) scan in planning post-surgical therapy and follow-up in patients with differentiated thyroid carcinoma (DTC). Four groups of DTC patients were considered: Group 1 comprised 122 patients with high serum thyroglobulin (s-Tg) levels and negative high-dose iodine-131 scan during follow-up who had previously undergone total thyroidectomy and 131I treatment. Group 2 consisted of 27 patients who had previously undergone total thyroidectomy and 131I treatment but were now considered disease-free; this group was considered as controls. Group 3 comprised 49 patients studied after total thyroidectomy but prior to 131I scan. Finally, group 4 consisted of 21 patients who had previously undergone partial thyroidectomy alone. MIBI scan, neck ultrasonography (US), and s-Tg measurements during suppressive hormonal therapy (SHT) were obtained in all patients. Neck and chest computed tomography (CT) or magnetic resonance imaging (MRI) was also performed in group 1 patients. In group 1, MIBI scan and US were very sensitive in detecting cervical lymph node metastases (93.54% and 89.24%, respectively). Furthermore, MIBI scan and US played a complementary role in several patients, yielding a global sensitivity of 97.84%. In contrast, CT/MRI sensitivity for cervical lymph node metastases was very low (43.01%). MIBI scan also showed a higher sensitivity than CT/MRI in detecting mediastinal lymph node metastases (100% vs 57.89%). Regarding distant metastases, MIBI scan provided results similar to those of conventional imaging (CT, MRI, 99mTc-methylene diphosphonate bone scan). In group 2, no false-positive cases were observed with MIBI scan (100% specificity). In group 3, MIBI scan correctly identified all the 131I-positive metastatic foci, except in two patients with micronodular pulmonary metastases that were visualised with 131I scan. In contrast, both MIBI scan and US showed low sensitivity (46.15% and 61.53%, respectively) compared with 131I scan in detecting thyroid remnants. s-Tg was increased in all patients with distant metastases but only in 56% of those with lymph node metastases. Furthermore, s-Tg was increased in 21.42% of patients with thyroid remnants alone (false-positive results). In group 4, MIBI scan was the only examination capable of detecting at an early stage a mediastinal lymph node metastasis in one patient. We conclude that the integrated MIBI scan/neck US protocol: (a) can be proposed as a first-line diagnostic procedure in the follow-up of DTC patients with high s-Tg levels and negative high-dose 131I scan, and (b) may be helpful in the follow-up of DTC patients who undergo partial thyroidectomy alone. Moreover, the combined MIBI scan/neck US/s-Tg protocol appears to be highly sensitive in identifying patients with metastatic disease after total thyroidectomy and prior to 1311 scan; consequently, it may play a prognostic role in distinguishing high-risk from low-risk DTC patients. However, due to the low sensitivity of MIBI scan and neck US in detecting thyroid remnants, this diagnostic approach cannot be used as a predictor of 131I scan results. Lastly, because of the high sensitivity of MIBI scan and neck US in revealing both functioning and non-functioning metastases, this integrated protocol might be helpful in the follow-up of high-risk DTC patients, particularly for the early detection of lymph node metastases in patients with undetectable s-Tg during SHT.

Oral iodized oil for correcting iodine deficiency: optimal dosing and outcome indicator selection.

Oral iodized oil is the major alternative to iodized salt for correcting endemic iodine deficiency. This study responds to a need for better guidelines in its use. Schoolchildren, aged 6-11 yr, from a severely iodine-deficient area of Algeria received iodized poppy seed oil (Lipiodol) in a single oral dose containing 120, 240, 480, or 960 mg iodine (groups A-D) or in an im injection of 480 mg iodine (group E). Thyroid volume by ultrasonography had not changed 395 days after treatment in groups A, B, and C, had decreased in groups D and E. Urinary iodine concentration rose rapidly from an initial median of 0.21 mumol/L, but fell below 0.79 mumol/L (the currently accepted level for indicating iodine deficiency) by 150 days for groups A and B, and by 395 days for groups C and D. Median serum TSH and T4 levels were normal before and after treatment, whereas high initial serum thyroglobulin values decreased in all groups after iodized oil treatment. For correcting iodine deficiency in children, we recommend single oral doses of Lipiodol containing 240 mg iodine for 6-month coverage or 480 mg for 12 months. These doses may not completely sustain iodine sufficiency, but will prevent the worst of the iodine deficiency disorders. Additionally, we conclude that the urinary iodine concentration is the most useful epidemiological indicator for assessing current iodine status, and thyroid volume and serum thyroglobulin levels are the best markers for assessing chronic effects.

Systematic inclusion of clinical and laboratory data improves diagnostic accuracy of fine-needle aspiration biopsy in solitary thyroid nodules.

In this study, we identified clinical and laboratory markers of malignant thyroid nodules and determined whether systematic inclusion of these data could improve diagnostic accuracy of fine-needle aspiration biopsy in solitary thyroid nodules. The patients were 24 men and 105 women who underwent surgical removal of solitary thyroid nodules and had adequate fine-needle aspiration biopsy performed prior to surgery. Including fine-needle aspiration biopsy's diagnosis of suspected of malignancy in the same category as malignancy, the sensitivity and specificity of fine-needle aspiration biopsy were 71.4% and 85.1%, respectively, with an accuracy of 82.2%. Using stepwise linear regression analysis, clinical data, i.e. increasing age, irregular nodule surface, hard consistency of nodule, and high serum thyroglobulin concentration, were associated with an increased risk of malignancy when the cytological result was excluded. When cytology was also considered, male sex, irregular nodule surface and high serum thyroglobulin concentration were found to be associated with an increased risk of malignancy. The diagnostic value of clinical data alone, even in combination with cytology or laboratory data, was inferior to that of fine-needle aspiration biopsy alone. The specificity and accuracy of fine-needle aspiration biopsy could be increased to 98.0% and 90.7%, respectively, whereas its sensitivity was decreased to 64.3% when these variables were considered in combination. Therefore, of fine-needle aspiration biopsy, clinical and laboratory data, fine-needle aspiration biopsy alone has the highest diagnostic value, which can be increased only when both clinical characteristics and serum thyroglobulin concentration are systematically included.