Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

Abstract

Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. The initial treatment consists of total thyroidectomy followed by ablation of thyroid remnants by radioiodine in most cases. As thyroid cells are the only source of thyroglobulin (Tg), circulating Tg serves as a biochemical marker of persistent or recurrent disease in the follow-up of DTC. Due to the suboptimal clinical detection rate of older Tg assays endogenous or exogenous thyrotropin (TSH) stimulations are recommended for unmasking occult disease. However, the development of new Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations, reflecting minimal amounts of thyroid tissue, even without the need for TSH stimulation. Even if the use of these assays still has not found its way in current clinical guidelines, such assays are now increasingly used in clinical practice. As serum Tg measurement is a technically challenging assay and criteria to define a 'highly sensitive' assay may be different, a good knowledge of the technical difficulties and interpretation criteria is of paramount importance for both clinical thyroidologists, laboratory physicians and scientists involved in the care of DTC patients.

Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids

“…In addition, it is important to bear in mind that before the measurement, the sample could require a pre-treatment such as mixing and centrifugation to discard cellular debris coming from blood and tissue contamination [78].…”

“…if undetectable FNA-marker is found, use dilution or batching to detect a possible "hook effect" Adopted cutoff Consider the method used by each individual center to determine the FNAmarker results and absence of formal support for this application by commercial manufacturers [6,69,78].…”

“…Moreover, in the interpretation of FNA marker levels, it is important to consider the clinical context of the patient, such as pre/post-thyroidectomy, histopathological diagnosis, and serum TSH concentration [78].…”

Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes

“…The published methods are based on peptide quantitation after tryptic digestion and immunocapture of Tgspecific peptide(s) (13)(14)(15)(16)(17)(18)(19)(20). Trypsin cleaves all proteins, including TgAb and other antibodies, thus eliminating them as interferences.…”

Serum thyroglobulin reference intervals in regions with adequate and more than adequate iodine intake

“…[31–33] Among these methods, interassay variation remains the principal challenge, as results can vary from 43% to 65% in healthy subjects. [24,34] Using the BCR 457 Reference Material (formerly named CRM 457) only reduces interassay variation by about 14% to 27% [6,35,36] ; therefore, it is important to develop local Tg RI.…”