Thyroglobulin Antibody and Thyroglobulin, IMA or RIA

Serum

3 mL (two tubes, 1.5 mL each tube)

2 mL (two tubes, 1 mL each tube) (Note: This volume does not allow for repeat testing.)

Red-top tube or gel-barrier tube

Thyroglobulin (Tg) measurement is intended to aid in monitoring for the presence of orthotropic and/or metastatic thyroid tissues in patients who have had thyroid gland ablation (using thyroid surgery with or without radioactivity). Measurement of thyroglobulin antibody (TgAb) is used to identify patient samples that may be affected by TgAb interference in the measurement of Tg. Quantitative TgAb concentrations can also serve as a surrogate tumor marker for DTC recurrence and for monitoring changes in tumor mass in certain patients.

Any changes in serum Tg concentrations should be interpreted in light of the total clinical presentation of the patient, including clinical history, data from additional testing and other appropriate information. Single measurement of thyroglobulin close to the limit of detection is of minimal value in assessing disease status. Serial determinations are required, and should be referenced to the postsurgical baseline Tg result when possible. Evaluation of increasing Tg levels over time are more clinically important.¹

Serial thyroglobulin (Tg) and/or thyroglobulin antibody (TgAb) testing on an individual patient should be performed by the same method for reliable interpretation.^2-4 When a change in Tg method is necessary, it is recommended to reëstablish a new baseline Tg level to then interpret further change over time.

As with all two-site "sandwich" immunoassays, some of the analytical limitations of Tg IMA include hook effects, human mouse antibody (HAMA), and anti-Tg interference. The Access Thyroglobulin assay does not demonstrate any "hook" effect for concentrations up to 40,000 ng/mL. The Access Thyroglobulin Antibody does not demonstrate any "hook" effect up to approximately 50,000 IU/mL. For samples that are Tg antibody positive, Tg will be measured using an RIA method,which is less prone to Tg antibody interference.

Immunometric assay (IMA and radioimmunoassay (RIA); Anti-Tg: Beckman Coulter immunometric assay; Tg IMA: Beckman Coulter immunometric assay; Tg RIA: Lab-developed radioimmunoassay LabCorp uses a dual Tg test strategy in an effort to minimize the potential effect of TgAb interference on Tg analysis. All specimens are initially assayed for TgAb by the highly sensitive Beckman Coulter IMA. Samples with TgAb below the detectable limit are assayed for Tg by a sensitive second-generation IMA (Beckman Coulter) with a relatively rapid turnaround time. Specimens with any measurable levels of TgAb are assayed by an RIA method performed at Endocrine Sciences, Calabasas Hills, Calif. This RIA is resistant to interference by TgAb but has a longer turnaround time of five to seven days.

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