Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous rare tumors. They are often slow-growing and patients can have very long survival, even at the metastatic stage. The ...evaluation of tumor progression and therapeutic responses is currently based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are being reexamined for NETs in the era of targeted therapies because tumor response to targeted therapies is rarely associated with shrinkage, as opposed to prolonged progression-free survival. Therefore, size-based criteria no longer seem to be suitable to the assessment of NET progression and therapeutic responses, especially considering targeted therapies. New imaging criteria, combining morphological and functional techniques, have proven relevant for other malignancies treated with targeted therapies. To date, such studies have rarely been conducted on NETs. Moreover, optimizing the management of NET patients also requires considering clinical, biological, and pathological aspects of tumor evolution. Our objectives herein were to comprehensively review current knowledge on the assessment of tumor progression and early prediction of therapeutic responses and to broaden the outlook on well-differentiated NETs, in the era of targeted therapies.
We compared the analytical and clinical performance of 3 porcine thyroid receptor antibody (TRAb) methods (1 second- and 2 new third-generation systems) with the conventional TRAb assay based on the ...human recombinant TSH receptor (hTRAK).
We obtained sera from 86 patients with untreated Graves disease (GD) and 71 healthy controls. We measured TRAb concentrations by radioreceptor assay using the hTRAK (Brahms) or the porcine TSH receptor (pRRA) from Beckman-Coulter, by electrochemiluminescence immunoassay (ECLIA) with the Elecsys/Cobas (Roche), and by ELISA using the Medizym TRAb clone (Medipan).
Between-run assay imprecision was < or =10% and < or =7.6% for hTRAK and ECLIA, but reached 14% and 14.9% for ELISA and pRRA, respectively. Maximal specificity and sensitivity close to 100% were obtained for hTRAK, ECLIA, and ELISA. pRRA failed to detect positive TRAbs in 5 GD patients. Although calibrated against the same reference standard 90/672, the assays displayed a high intermethod variability. The results were significantly higher by ECLIA and lower by ELISA and pRRA compared with hTRAK. Patients with ophthalmopathy had higher TRAb results by ELISA and pRRA than those without eye disease.
Second- and third-generation TRAb assays had similar diagnostic sensitivities in the diagnostic evaluation of GD. Despite the use of the same reference standard for calibration, high intermethod variability in TRAb assay results was seen in untreated GD patients. Assay harmonization is necessary for correct interpretation in the follow-up of Graves ophthalmopathy.
Calcitonin is the sensitive and specific marker of the medullary thyroid cancers. It is a diagnostic, pronostic and follow-up marker. Medullary thyroid cancer is a rare disease representing 4% of the ...thyroid cancers and occurring in 0.4% of nodular thyroid pathology. The use of sex specific adults normal ranges allows a better interpretation of the moderately elevated calcitonin levels. Hypercalcitoninaemia non due to medullary thyroid cancer are attributed mainly to male sex, tobacco use, overweight, renal failure and other endocrine tumors. CT is associated to carcinoembryonic antigen and possible procalcitonin assays. Calcitonin can be assayed in the wash-out fluid of the fine needle aspiration too. Stimulation tests give poor additional diagnostic information and are about to be abandoned.
ObjectiveThe objective of this study was to re-evaluate the adult CT reference values determined by five different immunoassays and by introducing criteria for selecting control subjects.DesignA ...prospective multicenter study.PatientsThree hundred and seventy-five clinically euthyroid subjects.MethodsWe used five different CT immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies.ResultsScreening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no CT was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between CT levels and age or body mass index (BMI) (primarily in men). The distribution of CT levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest CT values were around twice as high in men than women, and were higher in smokers than non-smokers.ConclusionIn clinical practice (and after having excluded the usual causes of raised CT levels), the interpretation of CT assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.
We assessed the analytical performance of the TSH and FT4 assays on ADVIA Centaur in a multicenter national evaluation.
A precision study and a method comparison were performed. Reference values ...stated by the manufacturer were checked from 379 normal subjects.
For TSH and FT4, the intra-assay CVs were below 2.3 and 5.2%, respectively, and the inter-assay CVs below 4.4% and 7.2%, respectively. Therefore, the precision and reproducibility were acceptable. Bland–Altman bias plots revealed good correlation and agreement with Cobas assays. TSH and FT4 data yielded reference ranges of 0.64–3.24mIU/L and 10.5–18.9pmol/L, respectively.
These assays demonstrate reliable characteristics. The reference ranges obtained can be used for interpretation of thyroid function.
•Siemens optimized the TSH3 and FrT4 assays to produce TSH3-UL and FT4 assays.•We assessed the analytical performance of these new assays on the ADVIA Centaur.•The TSH3-UL and FT4 Centaur assays show acceptable precision performances.•Bland–Altman bias plots revealed good correlation and agreement with Cobas.•Reference ranges for TSH and FT4 were checked from 379 healthy subjects.
Neuroendocrine tumors (NET) are rare heterogenous tumors which prevalence is increasing. Their features vary by anatomical location, functionality and hormonal production. Their management needs a ...multidisciplinary approach. Functional tumors develop characteristic clinical syndromes in contrast to non-functional tumors that are diagnosed fortuitously or at advanced stage. NET can secrete many specific and general biomarkers. CgA is the most sensitive general marker. Its value should be interpreted along with the renal function and the gastrin level. Some new biomarkers such as NTproBNP, proGRP and NET gene transcripts have been identified. The latter are not yet routine in clinical practice. We present In this review biological biomarkers involved in NET with a focus on the assays and their use in clinical practice.
Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of ...follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia.
Background: Coexistence of thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) with Graves' disease has been rarely reported. We describe a female patient displaying TSHoma with ...Graves' disease and who presented initially with inappropriate TSH values. Case Report: A 36-year-old woman presented with signs of thyrotoxicosis, small and vascular goiter and mild bilateral exophthalmos. Thyroid function tests showed hyperthyroxinemia and normal TSH values despite the use of different assays. Heterophile antibody testing result was negative. The patient underwent total right lobectomy with partial left lobectomy after 18 months of carbimazole treatment. Histology confirmed Graves' disease. Symptoms of thyrotoxicosis recurred 2 months later. Thyroid function tests showed hyperthyroxinemia and elevated TSH values. Investigations were consistent with a 10-mm TSHoma. The patient underwent a trans-sphenoidal tumor resection following preoperative lanreotide preparation. Histological examination and immunocytochemistry concluded to a pure TSH-producing tumor. There was no evidence of tumor recurrence after 18 years of follow-up. Conclusion: Association of TSHoma with Graves' disease should be carefully taken into account, especially when TSH values are not compatible with either the clinical history or other thyroid functions tests.
...TRAb measurements are used to investigate the etiology of hyperthyroidism when the diagno- sis is not clinically obvious; second, a declining TRAb concentration during long-term antithyroid drug ...therapy is suggestive of remission, although TRAb measurements can be misleading in 25% of such pa- tients; third, TRAb is used in the follow-up of pregnant women with a history or recent onset of Graves disease to evaluate the risk of fetal and neonatal thyroid dysfunction (1 ).
Adding insulin directly into infusion bags seems to be a useful method for controlling hyperglycemia in patients under ternary parenteral nutrition (TPN). Its efficacy is assessed by glycemic ...monitoring but few data are available on insulin stability in this situation. Among the various methods for quantifying insulin levels in human serum, the immunoassay ones seemed potentially appropriate for a TPN admixture containing high lipid concentrations. We sought to identify and validate which of two immunoassay methods was the better to quantify human insulin and consequently be adapted to studying its stability in a TPN admixture. Two immunoassay methods to quantify recombinant human insulin were assessed in industrial TPN: an immunoradiometric assay (IRMA) and an immunoelectrochemiluminometric assay (IECMA). Validation trials for both methods were based on the accuracy profile method. Interference with immunometric assays due to the high lipidic content of TPN was eliminated through an improved preparation protocol using a bovine serum albumin (BSA) diluted in phosphate buffer saline (PBS). The relative total error of IECMA varied from 1.74 to 4.52% while it varied from −0.32 to 8.37% with IRMA. Only IECMA provided an accuracy profile with a 95% confidence interval of calculated-tolerance limits falling between the chosen acceptance limits (i.e., total error ≤±10%). IECMA combined with a BSA dilution is a simple and semi-automatic method that provides an accurate quantification of human insulin in a TPN admixture without any interference from lipids.
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