Neck lymph node metastasis detection in patients with differentiated thyroid carcinoma (DTC) in long-term follow-up: a 131I-SPECT/CT study.

BACKGROUND: The identification of neck lymph node (LN) metastases represents a very important issue in the management of patients with differentiated thyroid carcinoma (DTC). To this purpose, in the present study, we used 131I-SPECT/CT as a diagnostic imaging procedure. METHODS: A consecutive series of 224 DTC patients with ascertained neck radioiodine-avid foci at 131I-SPECT/CT during long-term follow-up was evaluated. All patients had already undergone total thyroidectomy and radioiodine therapy and had been classified as follows: 62 at high risk (H), 64 at low risk (L) and 98 at very low risk (VL). 131I-Whole body scan (WBS) followed by SPECT/CT was performed in all cases. RESULTS: In the 224 patients, 449 neck iodine avid foci were ascertained at SPECT/CT, while 322 were evidenced at WBS in 165/224 patients. WBS classified as residues 263/322 foci and as unclear 59/322 foci; among the former foci SPECT/CT correctly characterized 8 LN metastases and 3 physiologic uptakes and among the latter, it pinpointed 26 LN metastases, 18 residues, and 15 physiologic uptakes. SPECT/CT also classified 127 foci occult at WBS as 59 LN metastases and 68 residues. Globally, SPECT/CT identified 93 LN metastases in 59 patients (26 H, 20 L, 13 VL), while WBS evidenced 34 in 25 cases. All 13 VL patients, T1aN0M0, 5 of whom with LN near sub-mandibular glands, had thyroglobulin undetectable or < 2.5 ng/ml. Globally, SPECT/CT obtained an incremental value than WBS in 45.5% of patients, a more correct patient classification changing therapeutic approach in 30.3% of cases and identified WBS false-positive findings in 8% of cases. CONCLUSIONS: 131I-SPECT/CT proved to correctly detect and characterize neck LN metastases in DTC patients in long-term follow-up, improving the performance of planar WBS. SPECT/CT routine use is thus suggested; its role is particularly relevant in patients with WBS inconclusive, VL, T1aN0M0 and with undetectable or very low thyroglobulin levels.

Blood presence of circulating oncofetal fibronectin mRNA, by RT-PCR, does not represent a useful specific marker for the management and follow-up of thyroid cancer patients.

BACKGROUND: Recent studies strongly suggest the use of oncofetal fibronectin (onfFN) mRNA in diagnostic follow-up and staging due to its very high specificity for thyroid cancers. Since the use of this marker has not been well established yet, particularly in the monitoring of minimal residual disease, we have tried to verify the diagnostic power of onfFN and its usefulness as a prognostic molecular marker. For this reason, we evaluated (by RT-PCR) the presence of onfFN mRNAs, not only in blood samples and thyroid tissues (both normal and neoplastic), but also in different biological fluids (such as K3-EDTA blood samples, saliva and urine) belonging to healthy individuals. METHODS: Molecular investigations, such as RT-PCR protocol, and sequencing of onfFN cDNAs evaluation of the above-mentioned samples were performed. RESULTS: The onfFN transcript was largely expressed in all benign and malignant thyroid tissues [differentiated thyroid carcinomas (DTCs)] tested as well as in a large number of biological fluids; in particular, 100% urine samples were positive for onfFN transcript as compared to the thyroglobulin (Tg) mRNA (75%), while saliva was always positive for onfFN and never for Tg. These findings indicate that onfFN cannot be considered a marker specific for thyroid cancer presence. Finally, Tg results were positive in a large part of the samples, but not always in concomitance with onfFN. CONCLUSIONS: We underline how the complexity of onfFN transcripts could affect the RT-PCR procedure. In addition, the presence of onfFN transcripts in several normal and cancer tissues, along with non-thyroid biological fluids or cells, does not allow the use of this marker for cancer monitoring.

Filter-Membrane-Based Ultrafiltration Coupled with Surface-Enhanced Raman Spectroscopy for Potential Differentiation of Benign and Malignant Thyroid Tumors from Blood Plasma.

OBJECTIVE: The objective of this study is to evaluate the performance and feasibility of surface-enhanced Raman spectroscopy coupled with a filter membrane and advanced multivariate data analysis on identifying and differentiating benign and malignant thyroid tumors from blood plasma. PATIENTS AND METHODS: We proposed a membrane filter SERS technology for the differentiation between benign thyroid tumor and thyroid cancer. That is to say, by using filter membranes with optimal pore size, the blood plasma samples from thyroid tumor patients were pretreated with the macromolecular proteins being filtered out prior to SERS measurement. The SERS spectra of blood plasma ultrafiltrate obtained using filter membranes from 102 patients with thyroid tumors (70 thyroid cancers and 32 benign thyroid tumors) were then analyzed and compared. Two multivariate statistical analyses, principal component analysis-linear discriminate analysis (PCA-LDA) and Lasso-partial least squares-discriminant analysis (Lasso-PLS-DA), were performed on the SERS spectral data after background subtraction and normalization, as well as the first derivative processing, to analyze and compare the differential diagnosis of benign thyroid tumors and thyroid cancer. RESULTS: SERS measurements were performed in blood plasma acquired from a total of 102 thyroid tumor patients (benign thyroid tumor N=32; thyroid cancer N=70). By using filter membranes, the macromolecular proteins in blood plasma were effectively filtered out to yield high-quality SERS spectra. 84.3% discrimination accuracy between benign and malignant thyroid tumor was achieved using PCA-LDA method, while Lasso-PLS-DA yields a discrimination accuracy of 90.2%. CONCLUSION: Our results demonstrate that SERS spectroscopy, coupled with ultrafiltration and multivariate analysis has the potential of providing a non-invasive, rapid, and objective detection and differentiation of benign and malignant thyroid tumors.

Use of 99mTc-sestamibi SPECT/CT when conventional imaging studies are negative for localizing suspected recurrence in differentiated thyroid cancer: a method and a lesson for clinical management.

PURPOSE: The detection of recurrent disease in differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple negative conventional imaging studies can be challenging, especially when 18F-FDG PET/CT scan is also negative. We report a patient and review the literature on the diagnostic use of 99mTc-sestamibi scans to identify the source of elevated or rising Tg in patients with negative conventional imaging including negative 18F-FDG PET/CT scans. PATIENT AND METHODS: A 73-year-old woman was referred for widely-invasive metastatic follicular thyroid cancer with bone metastasis to her left mandible. She had a total thyroidectomy, left mandibular resection, and 131I therapy of 145 mCi (5.4 GBq) and her subsequent unstimulated serum Tg level was 29 ng/ml (TgAb negative). At six months' follow-up, her stimulated Tg was 527 ng/ml (TSH 188 mIU/L, TgAb negative). All imaging studies performed within the prior 12 months were reported as negative for recurrence or metastasis; this included neck ultrasound, diagnostic radioiodine scan, chest CT and, 18F-FDG PET/CT. The patient was injected with 24.6 mCi (910 MBq) of 99mTc-sestamibi intravenously, and whole-body and SPECT/CT images were acquired. RESULTS: The 99mTc-sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponded to an occipital lytic bone lesion on the SPECT/CT. The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic follicular thyroid cancer. Five months post-surgery, the suppressed Tg was markedly reduced and remained stable at ~3.2 ng/ml. With the knowledge of the DTC recurrence location, the two sets of 18F-FDG images were re-evaluated. The more thorough and targeted interpretation underscored the importance of structured image reporting. The current literature on the utility of 99mTc-sestamibi scans when radioiodine, 18F-FDG PET/CT, and other imaging studies are negative is sparse and inconsistent. CONCLUSIONS: 99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and 18F-FDG PET/CT does not identify the source of elevated Tg levels in DTC.

[Hypercalcitoninemia and disorders of dentition development. A family study]. / Ipercalcitoninemia e disturbi della permuta dentale. Studio su un nucleo familiare.

INTRODUCTION: A lot of factors interfere in the physiopathology of the exfoliation of the primary teeth. One of the most important factors is bone shuffle which is due to osteoclastic activity; this activity is controlled by a hormonal equilibrium. CLINICAL CASE: The aim of the present study was to correlate primary teeth's exfoliation delay in two brothers with their hypercalcitoninemia. They had a positive familiar anamnesis for thyroid medullar cancer; this disease is notoriously associated with hypercalcitoninemia. CONCLUSIONS: The connection between a high basal and after-stimulation seric level of calcitonin and a lower activity of osteoclasis is evident. Thus, i also appeared evident to us the connection between the hormonal disease of the two children and the delay of exfoliation of their primary teeth. In these cases, it is important to control periodically the patients in order to prevent or to diagnose early isolated medullar thyroid cancer or a multiple endocrine adenomatosis.

The role of FDG-PET/CT in differentiated thyroid cancer patients with negative iodine-131 whole-body scan and elevated anti-Tg level.

AIM: In the follow-up of differentiated thyroid cancer (DTC) after a successful total-near total thyroidectomy and I-131 ablation therapy, anti-thyroglobulin antibodies (anti-Tg) may be persistently or progressively increased in the patients with an undetectable serum thyroglobulin (Tg) level. In these cases, further investigation was performed to search for recurrence/metastases. The aim of our study was clarifying the role of FDG-PET/CT in detecting recurrence/metastasis in patients with DTC with negative serum Tg and elevated anti-Tg level. MATERIALS AND METHODS: A total of 40 patients (32 female, 8 male; mean age: 43.15 years (22-65); mean age at diagnosis: 39.08 (16-64)) with DTC who had undetectable serum Tg and elevated anti-Tg level after a successful initial therapy were included in the study. All of the patients had serum anti-Tg of >40 IU/ml and underwent FDG-PET/CT to search for recurrence/metastasis. RESULTS: Twenty patients (50 %) had recurrence/metastasis on FDG-PET/CT while the other 20 had no pathologic findings. Of the 20 patients who had positive FDG-PET/CT, 12 had a histopathological final diagnosis of which 11 were true positive (TP) and 1 was false positive (FP). On the other hand, 16 of the 40 patients had a histopathological final diagnosis of which 11/16 had TP, 1/16 FP, 3/16 false negative (FN) and 1/16 true negative (TN) findings by PET/CT. The final diagnosis was made by clinical follow-up in the remaining 24 patients. Of these, 8 patients were PET positive, and in 1 (12.5 %) of 8 patients a decrease in serum anti-Tg level, in 2 (25 %) patients a saw-toothed pattern and in 5 (62.5 %) a progressive increase in the serum anti-Tg level were noted during the follow-up. Of the 16 of 24 patients who were diagnosed by clinical follow-up, in 8 a (50 %) decrease in serum anti-Tg level, in 6 (37.5 %) a saw-toothed pattern, and in 2 (12.5 %) a progressively increased anti-Tg level was seen. Of the 40 patients, 14 (35 %) had a diagnosis of recurrence/metastasis finally, with PET/CT detecting 11 (78.6 %) of them. CONCLUSION: The value of a persistently or progressively increased serum anti-Tg level in the follow-up of DTC in the prediction of recurrence/metastasis is controversial. However, it is reported that FDG-PET can be useful in the detection of recurrence/metastasis. We conclude from the available data that PET/CT can be effectively used in the detection of recurrence/metastasis in the follow-up of patients with DTC and negative serum Tg and a persistently/progressively increased anti-Tg level. Besides, one half of the patients were FDG negative, meaning that further studies are needed to assess the prognostic-clinical value of PET negativity.

Thyroid disorders. Part III: neoplastic thyroid disease.

This paper is part III of the series on thyroid disorders. Thyroid tumors are the most common endocrine neoplasms. Most of these tumors are benign hyperplastic or colloid nodules or benign follicular adenomas. However, 5% to 10% of the lesions that come to medical attention are carcinomas. A major clinical challenge is establishing which nodules are hyperplastic, benign, or malignant. History, clinical findings, ultrasonography, and fine-needle aspiration biopsy are the mainstays for diagnosis. There are 3 main histologic types of thyroid cancer: differentiated, medullary, and anaplastic. Differentiated lesions are subdivided into papillary, follicular, and Hurthle cell carcinomas. In addition, primary lymphoma may occur in the thyroid gland and other cancers may metastasize to the thyroid. An important neoplastic syndrome, multiple endocrine neoplasia type 2 (MEN2), involves medullary carcinoma of the thyroid gland. In 2002 there were 10 cases of thyroid cancer per 100 000 population. During the past 10 years the rate of thyroid cancer has been increasing 5% per year. The overall 10-year survival for papillary carcinoma is 80% to 90%, follicular carcinoma 65% to 75%, and medullary carcinoma 60% to 70%. The prognosis for anaplastic carcinoma is very poor and 5-year survival is rare. The dentist by inspection and palpation of the neck in the area of the thyroid gland may detect single or multiple lesions that may be benign or malignant. Patients with identified nodules or enlarged thyroid glands should be referred for diagnosis and treatment. Patients with thyroid cancer will benefit from the early detection and treatment of their lesions as early detection can lead to a cure or prolongation of their life.

Plasmapheresis rapidly eliminates thyroid hormones from the circulation, but does not affect the speed of TSH recovery following prolonged suppression.

OBJECTIVE: To report an attempt to shorten the preparation interval before radioactive iodine administration using plasmapheresis in a 77-year-old woman with a history of papillary thyroid carcinoma with local recurrence and lung metastases, in whom the administration of a high dose of radioactive iodine was intended as a desperate rescue procedure. METHODS: The patient was initially started on cholestyramine. Two days later, plasmapheresis was performed. RESULTS: Plasmapheresis rapidly decreased free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)). Serum FT(4) subsequently remained low, while FT(3) recovered the next day. Thyroid-stimulating hormone (TSH) reached 25 mIU/l in 14 days, which is within the time frame required to reach the target TSH level by withdrawing levothyroxine alone. CONCLUSION: Plasmapheresis is very effective in eliminating thyroid hormones from the circulation. However, it does not seem to accelerate thyrotroph recovery to a considerable extent after prolonged suppression.

Preparation for radioactive iodine administration in differentiated thyroid cancer patients.

OBJECTIVE: Because in recent years the practice of TSH suppression has changed, and thyroxine doses have been reduced significantly in the treatment of patients with low-risk differentiated thyroid cancer, the goal of this study was to determine the time needed to attain a target TSH level (of 30 mIU/l) following levothyroxine withdrawal in patients treated with thyroxine according to current guidelines, in anticipation of radioactive iodine (RAI) administration. DESIGN: Observational study. PATIENTS: Thirteen consecutive patients with differentiated thyroid cancer on suppressive doses of levothyroxine planned for RAI administration. Five of the patients received cholestyramine in an attempt to facilitate TSH recovery. MEASUREMENTS: Serum TSH, free-T3 and free-T4, at 3-4-day intervals. RESULTS: In 13 patients on suppressive doses of thyroxine, on 15 separate occasions, baseline TSH levels were between 0.01 and 0.4 mIU/l. The mean interval required to reach the target TSH concentration of at least 30 mIU/l was 17 days (95% CI 15-19; range 11-28 days). Cholestyramine had no effect on the rate of TSH recovery. Once TSH concentration became detectable, it increased exponentially; and once it reached the upper limit of normal, it rarely took more than 10 days to attain target level. CONCLUSIONS: Attaining target TSH level before radioactive iodine administration requires a considerably shorter time than is currently recommended. Reducing preparation time might improve patients' acceptance of the procedure.