Thyroglobulin Antibody and Thyroglobulin, IMA or RIA

Thyroglobulin (Tg) is synthesized exclusively by thyroid follicular cells as the precursor protein for thyroid hormone biosynthesis.^1,4,5 The serum Tg reflects the integrated sum of Tg released into the blood stream and is related to three factors:

1. Release of Tg into the blood stream is proportion to the mass of thyroid tissue present (from both normal and any tumor present).

2. The effect of any thyroid injury caused by inflammation associated with thyroiditis; radioactive iodine (RAI) therapy; fine needle aspiration (FNA) biopsy; or surgery.

3. The degree of TSH-receptor stimulation from endogenous TSH, recombinant human TSH (rhTSH), human chorionic gonadotropin (during pregnancy) or antibodies that stimulate the TSH receptor (Graves' disease).

Measurement of serum Tg is used primarily in the postoperative management and long-term surveillance of patients with DTC. Serum Tg concentrations reflect the residual mass of thyroid tissue present (normal remnant and/or tumor) and the effect of the three factors listed above.^1,4 Since Tg production is thyroid-specific but not tumor-specific, patient-related factors influence the interpretation of serum Tg concentrations. Postoperative serum Tg levels are related to the amount of residual normal and tumor tissue, recent thyroid injury, and the TSH status of the patient.

It should be noted that the thyroid tumors of some patients fail to secrete a detectable Tg concentration or may secrete abnormal Tg isoforms that are not detected by some assays used to measure Tg. Measurement of preoperative Tg levels can provide the clinician with insights regarding the tumor's Tg production and secretion and support the utility of postoperative Tg monitoring.

Thyroglobulin antibody (TgAb) is detected in approximately 10% of the general population and in 20% of patients with DTC.^4,6-8 Several studies have suggested that the quantitative TgAb concentrations can serve as a surrogate tumor marker for DTC recurrence and for monitoring changes in tumor mass in certain patients.⁹

Guidelines recommend that TgAb be measured in all specimens that are tested for Tg because TgAb positivity is associated with discordance in thyroglobulin values measured by radioimmunoassay (RIA) compared to values produced by immunometric assays (IMA) for Tg.¹⁰ TgAb interference with Tg-IMA measurements is associated with underestimation of Tg and the potential for reporting inappropriately low or undetectable values that can disguise the presence of disease.^5,10-12

Several lines of evidence suggest that the higher values of Tg assayed by RIA in the presence of TgAb may be more physiologically appropriate than the lower Tg values produced by ICMA methods. Patients with Graves' hyperthyroidism and TgAb often have unexpectedly low or undetectable IMA-Tg levels with RIA-Tg values are high and decrease in response to therapy.^4,13,14 Also TgAb-positive euthyroid individuals often have RIA-Tg within the range established for RIA-Tg in TgAb-negative euthyroid individuals. In contrast, IMAs produce low or undetectable Tg levels for many of the same individuals.¹⁰

Although RIA-Tg methods tend to be more resistant to TgAb interference than IMA-Tg methods, no immunoassay methodology for measurement of Tg is completely free from the potential for TgAb interference.¹⁵

Reference ranges established by testing normal, euthyroid subjects have little relevance when interpreting serum Tg concentrations in differentiated thyroid cancer (DTC) patients after thyroidectomy. Current guidelines recommend using a given assay's functional sensitivity (or LOQ) as the clinical threshold for distinguishing biochemically negative patients from those with residual Tg-producing tissue.⁵

• Beckman Coulter Tg IMA functional sensitivity (LQQ): 0.1 ng/mL

• Endocrine Sciences Radioimmunoassay for TgAb positive patients, functional sensitivity (RIA-Tg): 2.0 ng/mL

For the detection of interfering TgAb, the lower limit of detection (LOD) of the TgAb assay should be used. Even as low levels of TgAb, there may be interference with Tg-IMA assays.

• Beckman Coulter TgAb limit of detection (LOD): 0.9 IU/mL