Thyroglobulin is the most important and abundant protein in thyroid follicles and has been widely studied as a tumor marker of thyroid cancer recurrence and persistence. Tg is considered the material basis of thyroid hormone synthesis and does not participate in the regulation of thyroid hormone synthesis and secretion. This review summarizes the recent progress in the research of thyroid hormone synthesis and secretion regulation via a negative feedback regulation mechanism by the thyroid-hypothalamus-pituitary axis. Thyroglobulin can negatively regulate the synthesis of thyroid hormone by thyroid follicular cells and antagonize the positive regulation of thyrotropin TSH. The function of thyroid follicular cells is presumably a result of Tg and TSH interaction, and a follicular cycle model is proposed to explain the causes of follicular heterogeneity in glands. We also discuss the prospects and clinical significance of studies into the negative feedback regulation mechanism of the thyroid-hypothalamus-pituitary axis and compare two theories for this mechanism.
Feedback, Physiological ; Humans ; Hypothalamo-Hypophyseal System ; physiology ; Neoplasm Recurrence, Local ; Thyroglobulin ; metabolism ; Thyroid Gland ; physiology ; Thyroid Hormones ; metabolism ; Thyrotropin ; metabolism

OBJECTIVETo evaluate the usefulness of the thyroglobulin (Tg) level in adults as a nutritional biomarker of iodine status and to identify the factors related to the serum Tg level.

METHODSA cross-sectional study was conducted in adult populations of areas differing in iodine nutrition from three provinces (Autonomous Region) in China. Serum levels of thyroid hormones and Tg as well as thyroid autoantibodies were measured. The thyroid volume and nodule were measured by ultrasound. A multivariate linear regression analysis was used to assess iodine intake and other indeterminate factors associated with the serum Tg level.

RESULTSA total of 573 adults were recruited for this study. The serum Tg levels differed significantly among the three groups (22.27 μg/L, 9.73 μg/L and 15.77 μg/L in the excess, more-than-adequate, and deficient groups, respectively). The results of multivariate linear regression analysis indicate that excess and deficient iodine intake, goiter, thyroid nodule, hypothyroidism are significantly related with higher Tg level, and TgAb positivity is significantly related with lower serum Tg.

CONCLUSIONThe serum Tg level reflects abnormal thyroid function and is a sensitive functional biomarker of iodine nutrition status.

Adult ; Biomarkers ; blood ; China ; Cross-Sectional Studies ; Female ; Humans ; Iodine ; Male ; Middle Aged ; Thyroglobulin ; blood ; Thyroid Diseases ; blood ; Thyroid Gland ; metabolism

Renal metastasis of thyroid cancer is extremely rare. We report the case of a 62-year-old woman with Hürthle cell thyroid cancer (HCTC) with lungs, bones, and bilateral kidneys metastases. The renal metastatic lesions were clearly demonstrated by ¹³¹I whole body scan (WBS) with SPECT/CT. However, they exhibited false-negative results in ¹⁸F-FDG PET/CT, kidney ultrasonography, and contrast-enhanced CT scan. The findings imply that tumors have low glucose metabolism and are able to accumulate radioiodine, which is not commonly found in the relatively aggressive nature of HCTC. The patient received two sessions of 200 mCi ¹³¹I therapy within 6 months duration. There was complete treatment response as evaluated by the second post-therapeutic ¹³¹I SPECT/CT and serum thyroglobulin. To our knowledge, renal metastasis from HCTC with positive ¹³¹I but negative ¹⁸F-FDGuptake has not been reported in the literature. This case suggests that ¹³¹I SPECT/CTis useful for lesion localization and prediction of ¹³¹I therapy response.
Female ; Glucose ; Humans ; Kidney ; Lung ; Metabolism ; Middle Aged ; Neoplasm Metastasis ; Positron-Emission Tomography and Computed Tomography ; Sodium Iodide ; Sodium ; Thyroglobulin ; Thyroid Gland ; Thyroid Neoplasms ; Tomography, X-Ray Computed ; Ultrasonography ; Whole Body Imaging

PURPOSE: Ultrasound (US) and US-guided fine needle aspiration biopsies (FNAB) are considered the modalities of choice for assessing lymph nodes suspected of containing metastases, but the sensitivity of FNAB varies and is specific to the operator. We analyzed the risk of FNAB providing false negative results of lateral neck node metastasis, and evaluated diagnostic accuracy of FNAB, in patients with papillary thyroid cancer. MATERIALS AND METHODS: FNAB was performed in 242 patients suspected of having lateral neck node metastasis on preoperative imaging. Thyroglobulin in the fine-needle aspirate washout (FNA wash-out Tg) and computed tomography enhancement (Hounsfield units) were measured. Patients with negative results on FNAB were examined by intraoperative frozen section. The false negative and true negative groups were compared. RESULTS: Of the 242 patients, 130 were confirmed as having lateral neck node metastases. In 74 patients, the metastasis was identified by FNAB. False positive results were observed in 2 patients (0.8%) and false negatives in 58 (44.6%). Risk analysis showed that patient age <45 years (p=0.006), tumor size >1 cm (p=0.008) and elevated FNA wash-out Tg (p=0.004) were significantly associated with false negative results on FNAB. The accuracy of FNAB increased significantly when combined with FNA wash-out Tg (p=0.003). CONCLUSION: To reduce the false negative rate of FNAB, patient age (<45 years), tumor size (>1 cm) and FNA wash-out Tg (>34.8 ng/mL) should be considered in preoperative planning. Accuracy may be improved by combining the results of FNAB and FNA wash-out Tg.
Adolescent ; Adult ; Aged ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/*pathology/radiography/surgery ; False Negative Reactions ; Female ; Humans ; Lymph Nodes/*pathology/radiography ; Lymphatic Metastasis/*pathology/radiography ; Male ; Middle Aged ; Multivariate Analysis ; Preoperative Care ; Risk Factors ; Sensitivity and Specificity ; Thyroglobulin/metabolism ; Thyroid Gland/*pathology ; Thyroid Neoplasms/*diagnosis/*pathology/radiography/surgery ; Tomography, X-Ray Computed ; Young Adult

We evaluated the efficacy of recombinant human thyroid-stimulating hormone (rhTSH) versus thyroid hormone withdrawal (THW) prior to radioiodine remnant ablation (RRA) in thyroid cancer. A systematic search of MEDLINE, EMBASE, the Cochrane Library, and SCOPUS was performed. Randomized controlled trials that compared ablation success between rhTSH and THW at 6 to 12 months following RRA were included in this study. Six trials with a total of 1,660 patients were included. When ablation success was defined as a thyroglobulin (Tg) cutoff of 1 ng/mL (risk ratio, 0.99; 95% confidence interval, 0.96-1.03) or a Tg cutoff of 1 ng/mL plus imaging modality (RR 0.97; 0.90-1.05), the results of rhTSH and THW were similar. There were no significant differences when ablation success was defined as a Tg cutoff of 2 ng/mL (RR 1.03; 0.95-1.11) or a Tg cutoff of 2 ng/mL plus imaging modality (RR 1.02; 0.95-1.09). When a negative 131I-whole body scan was used solely as the definition of ablation success, the effects of rhTSH and THW were not significantly different (RR 0.97; 0.93-1.02). Therefore, ablation success rates are comparable when RRA is prepared by either rhTSH or THW.
Catheter Ablation ; Clinical Trials as Topic ; Databases, Factual ; Humans ; Iodine Radioisotopes/*therapeutic use ; Radiopharmaceuticals/*therapeutic use ; Recombinant Proteins/biosynthesis/genetics/therapeutic use ; Risk ; Thyroglobulin/analysis/metabolism ; Thyroid Neoplasms/*drug therapy/ultrasonography ; Thyrotropin/genetics/metabolism/*therapeutic use ; Treatment Outcome ; Whole Body Imaging

Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Follicular ; metabolism ; pathology ; surgery ; Bronchial Neoplasms ; metabolism ; secondary ; surgery ; Carcinoid Tumor ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Thyroglobulin ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology ; surgery ; Transcription Factors

OBJECTIVETo investigate the mechanism of thyroid cytotoxicity mechanism of ammonium perchlorate (AP).

METHODSThyroid cells were cultured in vitro to a certain stage and then exposed to AP (0, 5, 10, 20, 40, and 60 mmol/L) in culture solution; the cultured cells and supernatant were collected. Cell viability was measured by MTT assay; cell apoptosis was determined by flow cytometry; the concentration of thyroglobulin was measured by enzyme-linked immunosorbent assay; the lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, and so on were measured by colorimetry.

RESULTSThe cells exposed to 60 mmol/L AP for 12, 24, 48, and 72 h had cell viabilities of 74.93%, 42.26%, 2.66%, and 0.99%, respectively, and the cells exposed to 40 mmol/L AP for 24, 48, and 72 h had cell viabilities of 73.15%, 30.91%, and 3.03%, respectively, all significantly lower than that of the control group (100%)(P < 0.05 or P < 0.01). The overall apoptosis rate of all AP-exposed cells was significantly higher than that of the control group; the cells exposed to 20, 40, and 60 mmol/L AP had early apoptosis rates of 15.70%, 15.84%, and 16.96%, respectively, significantly higher than that of the control group (9.54%)(P < 0.05 or P < 0.01); the cells exposed to 60 mmol/L AP had a late apoptosis rate of 16.54%, significantly higher than that of the control group (6.11%)(P < 0.05 or P < 0.01). The cells exposed to 40 mmol/L AP had a significantly higher LDH activity than the control group (0.70 U/ml vs 0.55 U/ml, P < 0.01). The cells exposed to 5 mmol/L AP had a significantly higher MDA level than the control group (1.08 mmol/L vs 2.36 mmol/L, P < 0.05).

CONCLUSIONAP can markedly change the cell morphology and decrease the cell viability of thyroid cells, which may be because AP inhibits cell proliferation, induces cell apoptosis, and destroys cell membranes. However, AP does not result in significant oxidative damage to thyroid cells.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Humans ; Oxidative Stress ; Perchlorates ; toxicity ; Quaternary Ammonium Compounds ; toxicity ; Thyroglobulin ; metabolism ; Thyroid Gland ; drug effects ; metabolism ; pathology

PURPOSE: The purpose was to compare the frequency of metastatic and nonmetastatic lymph nodes diagnosed by fine needle aspiration biopsy cytology (FNAC) and thyroglobulin concentration from fine needle aspiration biopsy washout fluid (FNAB-Tg) in an indeterminate range (0.2-100 ng/mL), and to evaluate the most appropriate threshold value of FNAB-Tg in an indeterminate range. MATERIALS AND METHODS: We performed ultrasound-guided FNAB and FNAB-Tg in suspicious metastatic cervical lymph nodes of papillary thyroid carcinoma and performed surgery. Ninety-five lymph nodes with indeterminate values of FNAB-Tg ranging from 0.2-100 ng/mL in ninety-two patients were included in this study. The diagnostic performances in multiple Tg levels (0.7, 1.0, 5.0, 10.0, 20.0, 50.0) were evaluated to compare with FNAB cytology using sensitivity, specificity, and accuracy with area under the curve (AUC) analysis. RESULTS: Forty-two were metastatic lymph nodes and fifty three were nonmetastatic lymph nodes. FNAB-Tg ranged from 0.22 to 90.9 ng/mL in metastatic lymph nodes (mean; 34.3+/-33.3 ng/mL) and 0.20 to 56.7 ng/mL in nonmetastatic lymph nodes (mean; 4.9+/-11.1 ng/mL) (p<0.001). The most excellent diagnostic performance was displayed in 5 ng/mL of FNAB-Tg with AUC of 0.76, sensitivity, specificity, accuracy, 69.0, 83.0, and 76.8, respectively. However, there was no significant difference from 10 ng/mL FNAB. CONCLUSION: We ascertained that 5 ng/mL yielded the most excellent diagnostic performance among FNAB-Tg levels in the present setting with a large series with the indeterminate range (0.2-100 ng/mL) of FNAB-Tg values. These results need additional confirmation under different laboratory conditions.
Biopsy, Fine-Needle/*methods/standards/statistics & numerical data ; Body Fluids/metabolism ; Carcinoma, Papillary/*metabolism/*secondary/ultrasonography ; Humans ; Lymph Nodes/metabolism/pathology/ultrasonography ; Lymphatic Metastasis ; Retrospective Studies ; Sensitivity and Specificity ; Thyroglobulin/*metabolism ; Thyroid Neoplasms/*metabolism/*secondary/ultrasonography ; Ultrasonography, Interventional

Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is generally encouraging, a diagnostic dilemma is posed when an increasing level of serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using conventional imaging tools such as the iodine-131 whole-body scanning (the [131I] scan) or neck ultrasonography (US). The objective of the present study was to evaluate the diagnostic value of [124I]-PET/CT and [18F]-FDG-PET/CT in terms of accurate detection of both iodine- and non-iodine-avid recurrence, compared with that of conventional imaging such as the [131I] scan or neck ultrasonography (US). Between July 2009 and June 2010, we prospectively studied 19 DTC patients with elevated thyroglobulin levels but who do not show pathological lesions when conventional imaging modalities are used. All involved patients had undergone total thyroidectomy and radioiodine (RI) treatment, and who had been followed-up for a mean of 13 months (range, 6-21 months) after the last RI session. Combined [18F]-FDG-PET/CT and [124I]-PET/CT data were evaluated for detecting recurrent DTC lesions in study patients and compared with those of other radiological and/or cytological investigations. Nine of 19 patients (47.4%) showed pathological [18F]-FDG (5/19, 26.3%) or [124I]-PET (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients, disease management was modified in six (66.7%) and disease was restaged in seven (77.8%). In particular, the use of the described imaging combination optimized planning of surgical resection to deal with locoregional recurrence in 21.1% (4/19) of patients, who were shown to be disease-free during follow-up after surgery. Our results indicate that combination of [18F]-FDG-PET/CT and [124I]-PET/CT affords a valuable diagnostic method that can be used to make therapeutic decisions in patients with DTC who are tumor-free on conventional imaging studies but who have high Tg levels.
Adult ; Aged ; Aged, 80 and over ; Carcinoma/metabolism/*radionuclide imaging/surgery ; Female ; Fluorodeoxyglucose F18/chemistry/diagnostic use ; Follow-Up Studies ; Humans ; Iodine Radioisotopes/chemistry/diagnostic use ; Male ; Middle Aged ; Neck/ultrasonography ; Positron-Emission Tomography and Computed Tomography ; Prospective Studies ; Radiopharmaceuticals/chemistry/*diagnostic use ; Recurrence ; Thyroglobulin/blood ; Thyroid Neoplasms/metabolism/*radionuclide imaging/surgery ; Thyroidectomy ; Whole Body Imaging

Indeterminate cytology results increase the number of repetitive procedure and unnecessary surgery. This study was designed to find useful and simple predictive tools to differentiate malignant thyroid nodules from indeterminate nodules. We retrospectively enrolled 164 patients who had undergone thyroid surgery as a result of indeterminate cytology in the National Cancer Center. We reviewed patients' age at diagnosis, sex, preoperative biochemical markers such as thyroglobulin (Tg), anti-Tg antibody, free T4 and TSH level, and sonographical and pathological findings, which were subjected to statistical analysis. We found several clinical and sonographical predictive factors that showed significant differences. Young age, male, preoperative high Tg level, and hypoechoic nodule on sonography all increased cancer probability significantly in multivariate analysis. With a cut-off value of 187.5 ng/mL Tg, sensitivity and specificity were 54.8% and 90.1%, respectively (AUC 0.748, P < 0.001). In the case of nodule size > 1.7 cm, elevated serum Tg predicts the risk of malignancy; especially Tg > 70 ng/mL (odds ratio 3.245, 95% confidence interval 1.115-9.450, P = 0.038). Preoperative Tg levels had very high specificity in predicting thyroid cancer in case of suspicious follicular neoplasm. Therefore, Tg levels may be a useful marker for differentiating thyroid cancer from benign thyroid nodules in the cytological diagnosis of indeterminate nodules.
Adenocarcinoma, Follicular/*diagnosis/metabolism/pathology ; Adult ; Age Factors ; Aged ; Autoantibodies/blood ; Biological Markers/blood ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; Sex Factors ; Thyroglobulin/*blood ; Thyroid Nodule/ultrasonography