Basal Tg Levels Research Articles

Can the basal serum thyroglobulin level be used to predict the recombinant human TSH-stimulated thyroglobulin level in differentiated patients with thyroid cancer?

This study investigated the correlation between basal thyroglobulin (Tg) and recombinant human thyroid-stimulating hormone (rhTSH)-stimulated Tg in differentiated patients with thyroid cancer, and sought to determine whether the basal Tg level predicts the rhTSH-stimulated Tg level.We retrospectively enrolled 177 patients with papillary thyroid cancer (mean age = 44 years; 50 males, 127 females) who received rhTSH before radioiodine therapy (RIT). Serum Tg levels were measured 7 days before the 1st rhTSH injection (basal Tg) and on the days of RIT (rhTSH-stimulated Tg). Patients were divided into 3 groups according to rhTSH-stimulated Tg cut-off levels of 2, 5, and 10 ng/mL. The correlation between basal Tg and rhTSH-stimulated Tg levels was assessed, and whether basal Tg was useful in predicting the rhTSH-stimulated Tg level was determined.A significant positive correlation was observed between basal and rhTSH-stimulated Tg levels (|rho| = 0.48, P < .0001). The basal Tg level had significant diagnostic ability in predicting an rhTSH-stimulated Tg level of 2 ng/mL or higher, and the optimal basal Tg level for this prediction was 0.3 ng/mL (AUC = 0.77, P < .0001). A basal Tg level of 0.5 ng/mL was optimal for predicting rhTSH-stimulated Tg levels of 5 ng/mL or higher (AUC = 0.81, P < .0001), and of 10 ng/mL or higher (AUC = 0.82, P = .0171).The basal Tg level was significantly correlated with the rhTSH-stimulated Tg level. If the basal Tg level is >0.3 or 0.5 ng/mL, then the rhTSH-stimulated Tg level can be expected to be sufficiently high to necessitate clinical examination.

Accuracy of unstimulated Basal serum thyroglobulin levels in assessing the completeness of thyroidectomy.

BackgroundComplete excision is important for proper surgical treatment of thyroid disorders. Functional thyroid tissue can be identified based on the level of serum thyroglobulin (Tg), which is produced only by the thyroid follicular cells, and nuclear scan.MethodsSerum thyroid stimulating hormone (TSH), free thyroxin (FT4), basal (unstimulated) Tg and anti-Tg antibody (anti-Tg ab) were measured at the sixth postoperative month in 100 patients with benign thyroid disorders treated by total thyroidectomy. Thyroid nuclear scan was obtained to identify functional remnant of the thyroid gland. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the Tg levels in assessing thyroid remnant were calculated.ResultsPositive scan showed thyroid remnant in 23 patients, among whom 16 were Tg positive (true positive) and seven were Tg negative (< 0.5 ng/mL) (false negative). In these patients, the nuclear scan revealed pyramidal lobe remnants. In 77 patients with negative scan, the Tg levels were also negative (true negative), and the PPV, NPV, sensitivity, specificity and accuracy of the Tg levels were 100%, 92%, 70%, 100% and 93%, respectively.ConclusionsThe positive basal Tg (> 0.5 ng/mL) level accurately indicated the functional thyroid remnant after total thyroidectomy. The negative Tg (< 0.5 ng/mL) level supported complete excision of the thyroid gland. The surgical completeness of total thyroidectomy was accurately evaluated based on the serum Tg levels. Therefore, serum Tg levels should be measured in postoperative follow-up to determine the completeness of total thyroidectomy.

Therapeutic impact of 18F-FDG PET/CT in recurrent differentiated thyroid carcinoma

(18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) has proved effective in detecting recurrent or metastatic differentiated thyroid carcinoma (DTC) in the follow-up of operated DTC patients with high thyroglobulin (Tg) levels and negative findings on radioiodine whole-body scan. The aim of this retrospective study was to assess the impact of PET/CT on the planning of appropriate treatment for known recurrent disease in operated DTC patients. The study concerned 44 consecutive DTC patients (36 papillary, 8 follicular), who underwent total thyroidectomy and thyroid remnant ablation with (131)I and PET/CT. All patients had proven or strongly suspected recurrent disease judging from neck ultrasound (US) and fine-needle aspiration cytology, and detectable basal Tg levels. PET/CT findings were positive in 25/44 patients (56.81%) and negative in 19. A positive PET/CT result predicted resectable tumour recurrences in 19/25 patients, but also detected additional tumour sites that prompted changes to the treatment plan in 6/25 patients (24%). A negative PET/CT result led to clinical monitoring for 11/19 patients (57.89%). PET/CT can help select patients, who might benefit from a tailored therapy by improving the detection of local recurrences not apparent on neck US or metastases.

Long-Term Follow-Up of Patients With Differentiated Thyroid Cancer Who had Negative 131I Whole-Body Scan at First Evaluation After Treatment

The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglobulin (Tg) measurement and 131I whole-body scan (WBS). The first follow-up (6-12 months after initial treatment) shows the response to therapy, a prognostic factor.The aims of the study were to describe the clinical outcome during a long-term follow-up of patients with negative 131I WBS in the first evaluation, and to assess clinical and histological characteristics related to the outcome in this patient population. This retrospective study reviewed data from 209 patients followed at 2 Brazilian hospitals. A minimum of 10 years of follow-up was required. During mean follow-up of 13.7 ± 4.2 years, 20% of patients developed recurrence. At the end of follow-up, 21% of patients had persistent disease. The clinical and histological characteristics related to adverse outcomes (recurrence or persistent disease) were lymph node metastases at diagnosis, high risk according to American Thyroid Association (ATA) classification, and incomplete response to treatment. Stimulated Tg levels (under thyroid hormone withdrawal) and basal Tg levels (with thyroid hormone) greater than 10 ng/mL at first evaluation were associated with an adverse outcome. Negative WBS at first evaluation should not be used as an isolated prognostic factor. This must be considered together with histopathological (ATA classification, lymph node metastases) and clinical/laboratory characteristics (stimulated and basal Tg; response to therapy).

Successful Visualization of an Indeterminate Hepatic Metastasis From Thyroid Carcinoma Using Contrast-Enhanced CT and Contrast-Enhanced Ultrasound

A 76-year-old female underwent hemithyroidectomy in 2009 because of a thyroid tumor that was suspected to be papillary thyroid carcinoma. Histological examination revealed the tumor to be poorly differentiated papillary thyroid carcinoma with vascular invasion but without lymph node metastasis or local invasion. Serum levels of thyroglobulin (Tg) remained high ( 200 ng/mL) and increased thereafter postoperatively. However, no metastatic lesions were detected by chest-to-abdominal plain computed tomography (CT), bone scintigraphy, brain magnetic resonance imaging, upper abdominal ultrasound, or positron emission tomography-CT (Figure 1A). In addition, 131-I whole body scans after total thyroidectomy were negative (Figure 1B). Although not strictly indicated due to the high basal Tg level, a stimulation test was performed with 0.9 mg of recombinant human TSH for 2 consecutive days. Serum levels of Tg increased from 2853 to 11 579 ng/mL, suggesting the existence of viable thyroid cancer tissues. The patient underwent contrast-enhanced CT (CECT) to explore the rare sites of metastasis such as the pancreas (1) and bladder (2), which revealed a hepatic mass (Figure 2A). Contrast-enhanced ultrasound (CEUS) with a perflubutane microbubble agent (3) was used to successfully visualize the hepatic lesion. This was because the tumor had been undetectable 3 years before and was still indeterminate in the plain ultrasound (Figure 2, B and C). A diagnosis of thyroid carcinoma metastasis to the liver was made because of positive Tg and thyroid transcription factor-1 (TTF-1) immunostaining in the hepatic tumor specimens obtained by CEUS-guided tumor biopsy (Figure 2, D–F). The metastatic tumor was treated with transcatheter arterial chemoembolization in 2012, and serum levels of Tg dropped from 5865 to 2810 ng/mL within 2 months, although the tumor was not decreased significantly (Figure 2A, inset). This report suggests that indeterminate hepatic metastasis from thyroid carcinoma can be visualized by employing appropriate imaging modalities, including CECT and CEUS.

Stimulated tg level measurements may be avoided in differentiated thyroid carcinoma patients who have undetectable basal tg levels

Abstract Background: The aim of this retrospective study is to evaluate the diagnostic value of undetectable basal thyroglobulin (Tg) levels measured 6 months after ablative 131I treatment (AIT) in patients

Decreased serum vascular endothelial growth factor‐D levels in metastatic patients with differentiated thyroid carcinoma

Vascular endothelial growth factor-D (VEGF-D) has been identified as one of the lymphangiogenic growth factors involved in metastatic diffusion. The aim of this study is to evaluate the serum VEGF-D levels in patients with differentiated thyroid cancer at different conditions of disease. We studied prospectively the VEGF-D plasma levels in 96 subjects affected by differentiated thyroid cancer. The patients were divided into three groups according to the clinical and biochemical findings: patients with no evidence of disease (Cured), patients with pathological (>1 ng/ml) stimulated thyroglobulin (Tg) (Path-Tg/rhTSH) levels only after rhTSH and patients with elevated basal Tg levels (Path-Tg/LT4). The serum VEGF-D concentrations in patients of group Cured were not different from the controls, while group Path-Tg/rhTSH showed baseline serum VEGF-D levels significantly lower than group Cured and controls (P < 0·001 and P < 0·01, respectively). Moreover, the patients of group Path-Tg/LT4 showed median serum cytokine concentrations at baseline not significantly different from the patients of group Path-Tg/rhTSH. The rhTSH stimulation did not modify the difference in serum VEGF-D levels in patients of group Cured and group Path-Tg/rhTSH. Our data demonstrate that the VEGF-D serum levels are reduced in patients with metastases of differentiated thyroid cancer, regardless of the degree of metastatic spread. It is possible that some other molecule produced by the tumoral tissue could affect the VEGF-D physiologically produced of from different tissues, thus conducting to a decrease in the VEGF-D found in blood of patients with evidence of metastatic differentiated thyroid cancer.

Usefulness of repeated recombinant human thyrotropin-stimulated thyroglobulin test in the post-surgical follow-up of very low-risk patients with differentiated thyroid carcinoma.

The European Thyroid Association (ETA) and the American Thyroid Association (ATA) guidelines identify subgroups of patients affected by thyroid carcinoma in whom, due to a low risk of recurrence, radioiodine ablation is not indicated. These patients are referred to as "very low-risk" according to the ETA consensus and "low-risk" patients according to the ATA guidelines. The recommended post-surgical follow-up of these patients is based upon periodical measurements of serum thyroglobulin (Tg) on levothyroxine therapy and neck ultrasound (US). To evaluate the usefulness of recombinant human (rh)-TSH Tg test and its repetition 2-3 yr afterwards in very low-risk patients. We consecutively enrolled 32 patients with undetectable anti-Tg antibodies. Basal serum Tg levels was undetectable in all patients. Following rhTSH serum Tg remained undetectable in 23 (71.9%) patients (UP) and was >1.0 ng/ml in 9 (DP). US and whole body scan, revealed lymph node metastasis in 4/9 DP patients. A second rhTSH stimulation test (36.9±3.5 months later) was performed in all UP and in 5 DP patients without proven recurrences. All the UP and 4/5 formerly DP patients showed undetectable Tg stimulation. Our results suggest that rhTSH Tg test may be helpful in very low-risk patients, given its ability to differentiate those who may be considered "free of disease" from those who require further investigation and treatment. Repeated rhTSH Tg tests may be indicated only in patients with detectable serum Tg at prior stimulation testing.

Risk-Adapted Management of Differentiated Thyroid Cancer Assessed by a Sensitive Measurement of Basal Serum Thyroglobulin

Treatment and follow-up of patients thyroidectomized for differentiated thyroid carcinoma (DTC) mainly depends on the identification of the patient's risk of recurrence. Thyroglobulin (Tg) is the most important marker of persistent/recurrent disease. The recent introduction of a new, more sensitive Tg measurement allows for the early detection of the disease by measuring the basal (under L-T(4) therapy) serum Tg level without TSH stimulation. The goal of this study is to identify the basal serum Tg threshold value that indicates recurrent disease by using a second-generation Tg assay. A continuous series of 425 DTC patients, all thyroidectomized and treated with (131)I after surgery and having basal Tg of no more than 1.0 ng/ml, negative anti-Tg antibodies, and a recombinant human TSH-stimulated Tg measurement was retrospectively analyzed. The study took place at an academic hospital. The most accurate basal Tg value for predicting the presence of recurrent/residual disease was more than 0.15 ng/ml (sensitivity 87%, specificity 91%, negative predictive value 98.6%, and positive predictive value 47.8%). When the basal Tg level was no more than 0.15 ng/ml, the risk of disease presence was very low, even in patients classified at an intermediate or high risk. In contrast, when the basal Tg level was more than 0.15 ng/ml, the percentage of recurrent disease was relatively high (12.5% or one in eight cases) in low-risk patients. Basal Tg, measured using a second-generation Tg assay allows for the identification of DTC patients who are likely to remain disease free with great accuracy. This simple measurement, therefore, may be sufficient to assess the risk-adapted management of DTC patients.

Radio‐Guided Excision of Metastatic Lymph Nodes in Thyroid Carcinoma: A Safe Technique for Previously Operated Neck Compartments

Better follow-up of patients with papillary thyroid cancer (PTC) and more sensitive detection leads to detection of recurrences in the neck. Despite excellent outcomes, the major challenge is controlling locoregional recurrence. We aimed to investigate whether the radio-guided excision of metastatic lymph nodes makes it possible to find the affected lymph nodes in patients with previously operated neck compartments. This prospective study included 46 patients with recurrent/persistent PTC who had previously undergone operation of the neck compartment. Prior to operation, the pathologic node was localized by ultrasound (US) and radiotracer ((99m)Tc-labeled rhenium colloid) was injected directly into the pathologic node. Careful dissection was carried out following the area of maximum radioactivity until the metastatic lymph node(s) were identified and excised. One affected lymph node was removed in 17 patients, and more than one lymph node (affected or additional nodes) was removed in 29 patients. The median count from the lesion was significantly higher than values from the lesion bed (background activity) (16,886 counts/20s versus 52 counts/20s; p<0.001). During follow-up, four patients were lost to follow-up and 27 patients had negative US and basal thyroglobulin (Tg). Five patients had suspicious lymph nodes on the operated side. Although the basal Tg level remained above the normal limit, moderately high in 8 patients, no metastases were detected in the neck. Radio-guided excision of metastatic lymph nodes can be performed safely for the detection and excision of recurrent thyroid cancer in the central and lateral neck.

Impact de la TEP/TDM au 18F-FDG dans la prise en charge des patients atteints de cancer thyroïdien différencié

Aim 18F-FDG PET/CT by combining both metabolic and anatomical informations has proven to be an effective modality for detecting many types of cancer. Some differentiated forms of cancer like differentiated thyroid carcinoma (DTC) are less FDG avid and thus less easily detectable. Nevertheless 18F-FDG PET/CT has been proved useful in DTC especially in case of suspected recurrent disease with negative whole-body radioiodine scintigraphy ( 131I WBS) and elevated thyroglobulin (Tg) or thyroglobulin autoantibodies (AbTg) levels. Impact on clinical management after 18F-FDG PET/CT examinations has been analyzed in patients with suspected recurrent DTC in this retrospective study. Methodology Fifty-five 18F-FDG PET/CT were performed in 45 patients with suspected recurrent or residual disease either because of elevated Tg/AbTg levels ( n = 45) or uncertain conventional imaging ( n = 10) including 131I WBS, cervical echography and CT scan if necessary. 18F-FDG PET/CT results were compared with histopatology and/or clinical follow-up with evaluation of impact on clinical management. Results Twenty-nine exams were positive (53 %). There were 20 true-positive (TP) (14 locoregional relapses and six with distant metastases) and nine false-positive (FP) (all cervical). SUV max median values of hypermetabolic foci were significantly higher in TP (5.1) than in FP (2.8). Overall, 20 (36 %) 18F-FDG PET/CT directly affected clinical management resulting in 13 (65 %) new surgical operations. Sensitivity, specificity, predictive positive value, predictive negative value and accuracy of 18F-FDG PET/CT were estimated for the whole group (respectively 83 %, 71 %, 69 %, 85 % and 76 %) and for two subgroups depending on Tg level (less or more than 1.2 ng/mL). Discussion and conclusion 18F-FDG PET/CT is a powerful and useful tool in patients with suspected DTC recurrence or residual disease and should be systematically performed when basal Tg level is above 1.2 ng/mL. Thanks to given anatomical informations it can guide surgical re-operation.

Factors Influencing the Basal and Recombinant Human Thyrotropin-Stimulated Serum Thyroglobulin in Patients with Metastatic Thyroid Carcinoma

The serum thyroglobulin (Tg) level is the most sensitive marker for detecting residual thyroid carcinoma. We hypothesized that the basal and TSH-stimulated Tg levels in patients with metastatic thyroid carcinoma would reflect tumor volume, histological subtype, and location of metastatic lesions. A retrospective review of 417 thyroid cancer survivors undergoing evaluation for residual disease with the assistance of recombinant human TSH (rhTSH) was performed. In 169 patients with metastatic disease, we found that the basal Tg level directly correlated with the number of lesions, and that it was highest in patients with follicular and lowest in those with papillary thyroid carcinoma. The basal Tg level was highest in patients with bone metastases and lowest in those with cervical metastases. The fold increase in the serum Tg after rhTSH treatment was highest in papillary thyroid carcinoma and lowest in Hurthle cell carcinoma. The fold increase in Tg was not influenced by tumor volume or by the site of metastatic lesions. Multivariate analysis showed multiple interactions between factors, but did not identify one factor that significantly influenced basal Tg or fold increase. We conclude that the location and volume of metastases influence basal Tg, but not its responsiveness to rhTSH, whereas the histological type of carcinoma influences both basal Tg and responsiveness to rhTSH.

The use of recombinant human TSH in the follow-up of differentiated thyroid cancer: experience from a large patient cohort in a single centre.

Periodic evaluation of serum thyroglobulin (Tg) and whole body 131I imaging (131I-WBS) are essential in the follow-up of differentiated thyroid carcinoma (DTC); both diagnostic modalities require stimulation by high levels of TSH. Administration of recombinant human TSH (rhTSH) is an alternative to the withdrawal of thyroid hormone therapy. The aim of this study was to report our experience in the use of rhTSH for the management of patients with DTC. One hundred and four patients were enrolled in the study. A dose of 10 U of rhTSH therapy was injected intramuscularly for 2 consecutive days; 24 h after the second dose of rhTSH the patients were administered 4--5 mCi of 131I and, 48 h later, WBS was performed. In all patients, baseline mean serum Tg and TSH levels were 2.4 +/- 1.9 ng/ml and 0.0153 +/- 0.0232 mIU/l, respectively. Basal Tg levels were detectable in 58 out of 104 patients. After rhTSH injection, mean serum TSH levels rose to 122.67 +/- 47.36 mIU/l. Stimulated serum Tg levels increased to greater-than-or-equal 5 ng/ml and the 131I-WBS showed an uptake in 18 patients (17.4%). Among them there were three with bone metastases and one with brain metastases, who reported violent skeletal pain and a severe headache, respectively. These were caused by the growth of tumour mass of metastases induced by rhTSH administration. The use of rhTSH avoids the debilitating effects of hypothyroidism and its use successfully promotes iodine uptake and increases the sensitivity of serum Tg testing. The risk of causing serious side-effects recommends performing skull magnetic resonance and radionuclide bone scan in cases of suspected brain or skeletal metastases.

Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil.

Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to São Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency.

Long-term effect of iodized oil on serum thyroglobulin levels in endemic goitre patients.

Serum thyroglobulin (Tg) response to bovine TSH (bTSH) was evaluated in 44 goitrous patients (grades III and IV) living in conditions of chronic iodine (I) deficiency (iodine urinary excretion less than 40 micrograms I/g) and in 26 normal subjects. After the initial clinical evaluation and laboratory tests (bTSH test, T4, T3, anti-Tg and anti-microsomal antibodies) all goitrous patients received 1 ml i.m. of iodized oil (I-oil) and were followed up for 30 months. The bTSH test was repeated at 6, 12, 20 and 30 months after I-oil in 21 subjects. A marked reduction in goitre size was observed in 85% of the patients with a concomitant significant increase in the mean serum T4 and T3 concentrations, a significant fall in the mean serum TSH level and a significant decrease in the T3/T4 ratio. Goitrous patients had elevated serum basal Tg levels (55 +/- 8 SEM micrograms/l) and a significantly mean higher peak Tg value after bTSH (200 +/- 65 micrograms/l) as compared with normal subjects (respectively, 11 +/- 1.4 and 32 +/- 3.4 micrograms/l). Larger goitres (grade IV) had a significantly higher mean peak Tg response as compared with grade III goitres. Treatment with I-oil significantly reduced the mean peak Tg response to bTSH after 6 months (59 +/- 10 micrograms/l) but at 12 and 20 months the peak Tg response after the injection rose, respectively, to 110 +/- 19 micrograms/l and 92 +/- 14 micrograms/l (P less than 0.02 as compared with 6 months), returning to the normal range only at 30 months.(ABSTRACT TRUNCATED AT 250 WORDS)