Thyroglobulin measurement in the washout of fine needle aspirates for the diagnosis of suspicious cervical lymph nodes

Ultrasound-guided fine-needle aspiration cytology (FNAC) for suspicious cervical lymph nodes (CLN) is the gold standard technique for the identification of metastases from differentiated thyroid carcinomas. Thyroglobulin protein (Tgp) assay in the washout of needles employed for FNA biopsies (FNAB) has been reported to refine and support FNAC performances, especially in cases of inadequate sampling or cystic lymph nodes. In the present work, we evaluated the usefulness of routine measurement of Tgp in the FNAB washout of suspicious cervical lymph nodes (CLN), and its ability to increase the FNAC accuracy in the diagnosis of metastatic CLN. A case study of 45 CLN with histological diagnosis from 36 patients was analyzed. Histology showed metastases from papillary thyroid carcinomas (PTC) in 31 CLN, from anaplastic thyroid cancer (ATC) in 3 CLN, from medullary thyroid cancer (MTC) in 4 CLN, and metastases from extrathyroidal malignancies in 5 CLN. Two CLN analyzed were found to be non-neoplastic. The overall accuracy of FNAC was 82.9%, and that of Tgp was 91.1%, not statistically different. However, Tgp determination was found essential in 4 cases of metastatic CLN from DTC with inadequate cytology, and in 1 case in which the FNAC provided a false negative result. We demonstrated that FNAC and Tgp assay show similar diagnostic accuracies, and that Tgp measurement may represent the only available information in case of inadequate lymph node sampling or cystic lymph nodes

ENDOCRINE TUMOURS: Imaging in the follow up of differentiated thyroid cancer: current evidence and future perspectives for a risk-adapted approach

The clinical and epidemiological profiles of differentiated thyroid cancers (DTCs) have changed in the last three decades. Today's DTCs are more likely to be small, localized, asymptomatic papillary forms. Current practice is though moving towards more conservative approaches (e.g. lobectomy instead of total thyroidectomy, selective use of radioiodine). This evolution has been paralleled and partly driven by rapid technological advances in the field of diagnostic imaging. The challenge of contemporary DTCs follow up is to tailor a risk-of-recurrence-based management, taking into account the dynamic nature of these risks, which evolve over time, spontaneously and in response to treatments. This review provides a closer look at the evolving evidence-based views on the use and utility of imaging technology in the post-treatment staging and the short- and long-term surveillance of patients with DTCs. The studies considered range from cervical US with Doppler flow analysis to an expanding palette of increasingly sophisticated second-line studies (cross-sectional, functional, combined-modality approaches), which can be used to detect disease that has spread beyond the neck and, in some cases, shed light on its probable outcome. 

Expression of thyroglobulin on follicular dendritic cells of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma

Reportedly, thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Hashimoto's thyroiditis. However, it remains unknown which antigen is closely associated with thyroid MALT lymphoma. We examined whether B cell response to thyroglobulin (Tg), which is a common thyroid-specific autoantigen, is related etiologically to the pathogenesis of thyroid MALT lymphoma. Expression of human Tg antigens and Cluster of differentiation (CD) 35 was examined immunohistochemically in 15 cases of thyroid MALT lymphoma using paraffin-embedded, formalin-fixed tissue specimens. In all cases of thyroid MALT lymphoma, human Tg was detected immunohistochemically in the follicular epithelial cells and follicular dendritic cells (FDCs). These FDCs were positive by double immunostaining for anti-human Tg rabbit polyclonal antibody (Ab) and for CD35. Results showed that the Tg, a thyroid autoantigen, had immunostained the germinal center of the thyroid MALT lymphoma. The Tg was present in the FDCs, as revealed by the staining pattern of the germinal center;this fact was confirmed by double immunostaining of anti-human Tg mouse monoclonal Ab and anti-CD35 mouse monoclonal Ab. The results of our study suggest that Tg is an autoantigen that is recognized by thyroid MALT lymphoma cells.</p

Evaluation of the first automated thyroglobulin assay

The aim of this study was to investigate technical and analytical performance of the first automated thyroglobulin (Tg) assay (DPC-Immulite(R); Diagnostic Products Corporation, Los Angeles, USA). In imprecision studies using several human serum pools ranging from 21 to 58 replicates, a coefficient of variation of 9.0 % was obtained at a mean Tg concentration of 0.84 ng/ml and of 6.1 % at a Tg concentration of 62.1 ng/ml. In a method comparison with a non-automated assay (BRAHMS LUMItest Tg(R), BRAHMS, Berlin, Germany) using 383 sera of 303 patients with thyroid carcinoma, regression analysis according to Passing and Bablock yielded in the following equation: Immulite Tg=1.6 x BRAHMS Tg - 0.1 ng/ml (Pearson's r=0.979). Sera obtained from 59 patients with thyroid carcinoma enabled comparative follow-up studies; in all cases qualitative agreement was found with regard to increase or decrease of serum Tg; in eight cases, however, Tg was detected with the Immulite assay but not with the BRAHMS assay. Further follow-up proved the presence of thyroid tissue in these patients. From these and further methodological data (dilution linearity, interference studies, carry-over study, high-dose hook properties, and short report time) it is concluded that the DPC-Immulite Tg assay meets the requirements of routine diagnostic use

Serum thyroid hormone antibodies are frequent in patients with polyglandular autoimmune syndrome type 3, particularly in those who require thyroxine treatment

Polyglandular autoimmune syndrome (PAS) type 3 consists of autoimmune thyroid disease (AITD) coexisting with ≥1 non-thyroidal autoimmune disease (NTAID) other than Addison’s disease and hypoparathyroidism. We evaluated the prevalence and repertoire of thyroid hormones antibodies (THAb) in PAS-3 patients. Using a radioimmunoprecipation technique, we measured THAb (T3IgM, T3IgG, T4IgM, and T4IgG) in 107 PAS-3 patients and 88 controls (patients with AITD without any NTAID). Based on the selective coexistence of AITD with one NTAID (chronic autoimmune gastritis, non-segmental vitiligo or celiac disease), patients were divided into group 1 (chronic autoimmune gastritis positive, n = 64), group 2 (non-segmental vitiligo positive, n = 24), and group 3 (celiac disease positive, n = 15). At least one of the four THAb was detected in 45 PAS-3 patients (42.1%) and 28 controls (31.8%, P = 0.14), with similar rates in the three PAS-3 groups. The rates of T3Ab, T4Ab, and T3 + T4Ab were similar in groups 1 and 2, while in group 3, T3Ab was undetected (P = 0.02). In PAS-3 patients, the rate of levothyroxine treatment was greater in THAb-positive patients compared to THAb-negative patients (76.7 vs. 56.1%, P = 0.03, RR = 1.4, 95% CI 1.03–1.81). Not unexpectedly, levothyroxine daily dose was significantly higher in group 1 and group 3, namely in patients with gastrointestinal disorders, compared to group 2 (1.9 ± 0.4 and 1.8 ± 0.3 vs. 1.5 ± 0.2 μg/kg body weight, P = 0.0005 and P = 0.004). Almost half of PAS-3 patients have THAb, whose repertoire is similar if chronic autoimmune gastritis or celiac disease is present. A prospective study would confirm whether THAb positivity predicts greater likelihood of requiring levothyroxine treatment

Involvement of Mhc Loci in immune responses that are not Ir-gene-controlled

Twenty-nine randomly chosen, soluble antigens, many of them highly complex, were used to immunize mice of two strains, C3H and B10.RIII. Lymphnode cells from the immunized mice were restimulated in vitro with the priming antigens and the proliferative response of the cells was determined. Both strains were responders to 28 of 29 antigens. Eight antigens were then used to immunize 11 congenic strains carrying different H-2 haplotypes, and the T-cell proliferative responses of these strains were determined. Again, all the strains responded to seven of the eight antigens. These experiments were then repeated, but this time -antibodies specific for the A (AA) or E (EE) molecules were added to the culture to block the in vitro responsiveness. In all but one of the responses, inhibition with both A-specific and E-specific antibodies was observed. The response to one antigen (Blastoinyces) was exceptional in that some strains were nonresponders to this antigen. Furthermore, the response in the responder strains was blocked with A-specific, but not with E-specific, antibodies. The study demonstrates that responses to antigens not controlled by Irr genes nevertheless require participation of class II Mhc molecules. In contrast to Ir gene-controlled responses involving either the A- or the E-molecule controlling loci (but never both), the responses not Ir-controlled involve participation of both A- and E-controlling loci. The lack of Ir-gene control is probably the result of complexity of the responses to multiple determinants. There is thus no principal difference between responses controlled and those not controlled by Ir genes: both types involve the recognition of the antigen, in the context of Mhc molecules

Methods to assess iron and iodine status

Four methods are recommended for assessment of iodine nutrition: urinary iodine concentration, the goitre rate, and blood concentrations of thyroid stimulating hormone and thyroglobulin. These indicators are complementary, in that urinary iodine is a sensitive indicator of recent iodine intake (days) and thyroglobulin shows an intermediate response (weeks to months), whereas changes in the goitre rate reflect long-term iodine nutrition (months to years). Spot urinary iodine concentrations are highly variable from day-to-day and should not be used to classify iodine status of individuals. International reference criteria for thyroid volume in children have recently been published and can be used for identifying even small goitres using thyroid ultrasound. Recent development of a dried blood spot thyroglobulin assay makes sample collection practical even in remote areas. Thyroid stimulating hormone is a useful indicator of iodine nutrition in the newborn, but not in other age groups. For assessing iron status, haemoglobin measurement alone has low specificity and sensitivity. Serum ferritin remains the best indicator of iron stores in the absence of inflammation. Measures of iron-deficient erythropoiesis include transferrin iron saturation and erythrocyte zinc protoporphyrin, but these often do not distinguish anaemia due to iron deficiency from the anaemia of chronic disease. The serum transferrin receptor is useful in this setting, but the assay requires standardization. In the absence of inflammation, a sensitive method to assess iron status is to combine the use of serum ferritin as a measure of iron stores and the serum transferrin receptor as a measure of tissue iron deficiency