DIAGNOSIS OF ENDOCRINE DISEASE: Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper

Abstract

Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous TSH is recommended by current clinical guidelines to detect occult disease with a maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive 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 without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.

Radioiodine treatment after surgery for differentiated thyroid cancer: a reasonable option

“…First, interference from TgAb compromises the use of serum Tg as a tumor marker in up to 25% of DTC patients by reducing Tg measurement results in immunometric methods [31]. Second, interferences by heterophilic antibodies, as well as the so-called Bhigh-dose hook effect,^or decreased immunological reactivity or changes of the structural conformation of the Tg molecule may in rare instances lead to report inappropriately low serum Tg values in sera with high Tg concentrations [32]. The importance of these interferences has been documented by analyzing sera from 47 DTC patients presenting undetectable serum Tg, but residual 131 I uptake on a PT-WBS [33].…”

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

“…Issues of commutability of the BCR ® 457 material and the need for harmonization have yet to be addressed (discussed elsewhere in this article). Due to the lack of agreement between different immunoassays it has been recommended that patients should be followed up using the same assay [5,6,11,12]. If an assay change is required then dual reporting of patient results for a period of time to allow comparison of results by re-baselining serum Tg quantitation by the new assay is suggested.…”

“…If an assay change is required then dual reporting of patient results for a period of time to allow comparison of results by re-baselining serum Tg quantitation by the new assay is suggested. In addition, it is suggested that clinical decision limits should be assay specific [11]. Laboratories will be familiar with the necessary experiments to be performed to verify assay performance [13,14], namely assessment of linearity, measuring range, trueness (measurement bias), comparability through patient comparison studies, limit of detection/limit of quantitation/functional sensitivity.…”

“…For longitudinal consistency of clinical care, consecutive measurements of Tg concentrations should be performed in the same laboratory using the same assay each time. If an assay change is unavoidable, a new baseline of the individual patient's serum Tg concentrations should be established through parallel Tg measurements using both the old and the new assay [11]. Furthermore, internal and external quality control programs, including samples at low and very low Tg concentrations, are of pivotal importance for checking the precision, reproducibility (internal quality control) and accuracy (e.g., lack of bias of analytical results) of assays to ensure optimal patient care.…”

“…Further improvements in assay technology have however recently resulted in new highly sensitive Tg (hsTg) assays [8,9]. From an increasing number of studies in the literature it appears that these assays are in fact sufficiently sensitive to obviate the need for TSH stimulation in most DTC patients [10,11]. Therefore, the increasing adoption of these assays in clinical practice has considerable implications, such as a reduction of costs of DTC follow-up or avoidance of hypothyroidism.…”