ABSTRACT
ABSTRACT Thyroglobulin (Tg) is the major glycoprotein produced by the thyroid gland, where it serves as a template for thyroid hormone synthesis and as an intraglandular store of iodine. Measurement of Tg levels in serum is of great practical importance in the follow-up of differentiated thyroid carcinoma (DTC), a setting in which elevated levels after total thyroidectomy are indicative of residual or recurrent disease. The most recent methods for serum Tg measurement are monoclonal antibody-based and are highly sensitive. However, major challenges remain regarding the interpretation of the results obtained with these immunometric methods, particularly in patients with endogenous antithyroglobulin antibodies or in the presence of heterophile antibodies, which may produce falsely low or high Tg values, respectively. The increased prevalence of antithyroglobulin antibodies in patients with DTC, as compared with the general population, raises the very pertinent possibility that tumor Tg may be more immunogenic. This inference makes sense, as the tumor microenvironment (tumor cells plus normal host cells) is characterized by several changes that could induce posttranslational modification of many proteins, including Tg. Attempts to understand the structure of Tg have been made for several decades, but findings have generally been incomplete due to technical hindrances to analysis of such a large protein (660 kDa). This review article will explore the complex structure of Tg and the potential role of its marked heterogeneity in our understanding of normal thyroid biology and neoplastic processes.
Subject(s)
Humans , Protein Processing, Post-Translational , Thyroid Diseases , Thyroglobulin/metabolism , Biomarkers, Tumor/blood , Glycosylation , Halogenation , Phosphorylation , Thyroglobulin/chemistry , Thyroid Diseases/blood , Thyroid Diseases/diagnosis , Thyroid Diseases/etiology , Thyroid Diseases/prevention & control , Thyroid Hormones/biosynthesisABSTRACT
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 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 (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.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Biopsy, Fine-Needle , Carcinoma/diagnosis , False Negative Reactions , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Multivariate Analysis , Preoperative Care , Risk Factors , Sensitivity and Specificity , Thyroglobulin/metabolism , Thyroid Gland/pathology , Thyroid Neoplasms/diagnosis , Tomography, X-Ray ComputedABSTRACT
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.
Subject(s)
Humans , Biopsy, Fine-Needle/methods , Body Fluids/metabolism , Carcinoma, Papillary/metabolism , Lymph Nodes/metabolism , Lymphatic Metastasis , Retrospective Studies , Sensitivity and Specificity , Thyroglobulin/metabolism , Thyroid Neoplasms/metabolism , Ultrasonography, InterventionalABSTRACT
A 50-yr-old male presented a thyroid mass with dysphasia and hoarseness. He underwent total thyroidectomy and neck node dissection. Pathologically, the tumor had two distinct tumor components with intermingled areas: follicular variant of papillary carcinoma and mucoepidermoid carcinoma. Mucoepidermoid carcinoma composed of columnar cells, mucocytes, and squamoid cells showing solid and cystic lesion. Several small cysts lined by benign ciliated columnar epithelia suggesting that this tumor had originated from solid cell nest were seen around the tumor. By immunohistochemistry, columnar cells and squamoid cells in mucoepidermoid carcinoma were positive for cytokeratin but negative for thyroglobulin, TTF-1 and calcitonin. Positivity of p63 was seen in squamoid cells and basal cells of cysts. Some mucocytes are CEA positive. Tumor cells of papillary carcinoma are positive for TTF-1, thyroglobulin but negative for CEA, calcitonin and p63.
Subject(s)
Humans , Male , Middle Aged , Calcitonin/metabolism , Carcinoma, Mucoepidermoid/diagnosis , Carcinoma, Papillary/diagnosis , Immunohistochemistry , Keratins/metabolism , Membrane Proteins/metabolism , Nuclear Proteins/metabolism , Thyroglobulin/metabolism , Thyroid Neoplasms/diagnosis , Transcription Factors/metabolismABSTRACT
We present a case of a 40-yr-old woman diagnosed with a primary malignant struma ovarii. The patient was admitted with the complaint of pelvic pain and a large pelvic mass in the mid-portion of lower abdomen on gynecological examination. Pre-operative tumor markers and routine biochemistry were unremarkable. She was treated with total abdominal hysterectomy and right salpingo-oopherectomy. Post-operatively, she was diagnosed with a malignant struma ovarii through the usage of histopathological criteria similar to the guidelines for primary thyroid gland disease. The patient was subsequently performed left salpingo-oopherectomy and retroperitoneal pelvic lympadenectomy for re-staging. Although, left ovary and lymph nodes were histopathologically normal, she was offered thyroidectomy but she refused to accept the offer. Thyroglobulin level was monitored in the post-operative period. She is free of the disease for 18 months.
Subject(s)
Adult , Female , Humans , Hysterectomy , Ovarian Neoplasms/diagnosis , Ovariectomy , Struma Ovarii/diagnosis , Thyroglobulin/metabolismABSTRACT
OBJECTIVE: Our goals were to determine the added value of fine-needle aspiration biopsy (FNAB)-thyroglobulin (Tg) measurements over FNAB-cytology alone for diagnosing metastatic nodes, and to determine whether the ultrasound features of lymph nodes can be used to identify lymph nodes that may benefit from FNAB-Tg measurement in patients with papillary thyroid cancer. MATERIALS AND METHODS: We retrospectively evaluated 76 surgically proven cervical lymph nodes. Twenty-nine patients were awaiting surgery and 18 patients had undergone thyroid surgery for papillary thyroid cancer. Ultrasound-guided FNAB and Tg measurements were performed and the ultrasound features were evaluated. RESULTS: The accuracies, sensitivities, and specificities of FNAB-cytology, FNAB-Tg, and combined FNAB-Tg/cytology were 90%, 80%, and 100%; 92%, 95%, and 90%; and 93%, 96%, and 90%, respectively. The diagnostic sensitivity of FNAB-Tg for metastatic nodes was significantly higher than that of FNAB-cytology (p = 0.011). Furthermore, combined FNAB-Tg/cytology significantly increased sensitivity (p = 0.002) and accuracy (p = 0.03) as compared with FNAB-cytology. CONCLUSION: Combined FNAB-Tg/cytology is significantly more sensitive and accurate at detecting metastatic nodes than FNAB-cytology alone. FNAB-Tg was better at diagnosing metastases in small lymph nodes.
Subject(s)
Humans , Biopsy, Fine-Needle , Carcinoma, Papillary/pathology , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis/diagnosis , Retrospective Studies , Sensitivity and Specificity , Thyroglobulin/metabolism , Thyroid Neoplasms/pathology , Ultrasonography, InterventionalABSTRACT
Members of the inhibitors of differentiation (Id) family of helix-loop-helix (HLH) proteins are known to play important roles in the proliferation and differentiation of many cell types. Thyroid-stimulating hormone (TSH) regulates proliferation and differentiation by activating TSH receptor (TSHR) in thyrocytes. In this study, we found that Id2, one of the Id family proteins, is a major target for regulation by TSH in FRTL-5 thyroid cells. TSH rapidly increases the Id2 mRNA level in FRTL-5 thyroid cells but the Id2 protein showed biphasic regulatory patterns, being transiently reduced and subsequently induced by TSH treatment. Transient reduction of Id2 protein was noted within 2 hr of TSH treatment and was mediated by proteasomal degradation. Moreover, reduced Id2 expression correlated with the activity of the phosphatidylinositol 3 kinase pathway, which is activated by TSH. Although TSH increases the activity of the Id2 promoter, TSH-induced activation of this promoter was independent of c-Myc. Id2 did not alter TTF-1- and Pax-8-mediated effects on the regulation of the Tg promoter. Thus, in summary, we found that TSH regulates Id2 expression, but that Id2 does not alter the expression of thyroid-specific genes, such as Tg, in FRTL-5 thyroid cells.
Subject(s)
Animals , Cattle , Rats , Phosphatidylinositol 3-Kinase/metabolism , Cell Differentiation , Cell Proliferation , Gene Expression Regulation , Inhibitor of Differentiation Protein 2/metabolism , Insulin/metabolism , Paired Box Transcription Factors/metabolism , Promoter Regions, Genetic , Proto-Oncogene Proteins c-myc/metabolism , Thyroglobulin/metabolism , Thyroid Gland/cytology , Thyrotropin/metabolismSubject(s)
Adolescent , Autoantibodies/analysis , Autoantigens/metabolism , Autoimmunity , Chemoprevention , Child , Female , Goiter, Endemic/enzymology , Humans , Hypothyroidism/enzymology , Iodide Peroxidase/metabolism , Iodine/deficiency , Iron-Binding Proteins/metabolism , National Health Programs , Prevalence , Sodium Chloride, Dietary/standards , Sri Lanka/epidemiology , Thyroglobulin/metabolismABSTRACT
Os avanços da biologia molecular e o emprego de técnicas de identificaçäo de porçöes de DNA codificadoras para proteínas importantes na síntese, armazenamento, transporte e açäo periférica dos hormônios tireoideos, permitiram a elucidaçäo, a nivel molecular, da etiologia de várias condiçöes genéticas da tireóide. Em pacientes com defeito na peroxidase tireóidea (TPO) observou-se a presença de polimorfismo (RFLP) com a endonuclease Bgl-I que se segrega, em 2 alelos, com o fenótipo com bócio, hipotireoidismo e teste de perclorato positivo. Em defeitos da tireoglobulina (Tg), observou-se nível quantitativamente baixo de Tg, concomitante com a virtual ausência da RNA mensageiro para a Ig. Por outro lado, a ausência de incorporaçäo de ácido siálico na molécula de Tg, produz proteína com defeito estrutural que impede a síntese adequada de T3 e T4. Tais defeitos da Tg säo igualmente encontrados em animais com bócio congênito (gados bovino e caprino, e camundongos cog/cog). A presença de mutaçäo puntiforme no nucleotídeo 281 do exon 5 do RNA da globulina carreadora de T4 (TBG) leva a expressäo genética de proteína instável, com queda da TBG sérica. O efeito nos receptores nucleares de T3 estäo ligados ao gene codificador (c-erb-A-beta) localizado no cormossoma 3. A presença de polimorfismo EcorRV nos indivíduos, sugere gene mutante codificando proteína que poderia näo fixar T3 ou produzir proteína anômala com atividade bloqueadora da açäo de T3 impedindo a fixaçäo nuclear