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Test ID IETG Interference Evaluation Heterophile, Thyroglobulin Tumor Marker, Serum

Ordering Guidance

If interference or heterophile testing is not required, order HTG2 / Thyroglobulin, Tumor Marker, Serum.


For fine-needle aspirate specimens, order TFNAB / Thyroglobulin, Tumor Marker, Fine-Needle Aspiration Biopsy Needle Wash.

Specimen Required

Patient Preparation: For 12 hours before specimen collection do not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Collection Container/Tube: Red top (serum gel/SST are not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 2.5 mL

Profile Information

Test ID Reporting Name Available Separately Always Performed
TGII TG, Interference Interpretation No Yes
TGQN Thyroglobulin, Tumor Marker, S Yes, (Order HTG2) Yes
TGABI Thyroglobulin Antibody, S Yes, (Order HTG2) Yes
TGMS Thyroglobulin, Mass Spec., S Yes Yes

Testing Algorithm

Heterophile antibody evaluation consists of comparison of thyroglobulin (Tg) concentrations obtained by immunoassay with the following:

-Tg concentrations following pretreatment with commercial heterophile blocking reagents

-Tg concentrations obtained by mass spectrometry

-Tg concentrations obtained by serial dilutions of the sample

In all samples the presence of anti-thyroglobulin antibodies are evaluated.

Method Name

TGQN/TGABI: Immunoenzymatic Assay

TGMS: Tryptic Protein Fragmentation, purified with Immunocapture, Analysis by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

(This service is performed pursuant to an agreement with SISCAPA Assay Technologies Inc. covering US Patent 7,632,686)

TGII: Medical Interpretation

Reporting Name

Interference Eval, Heterophile, TG

Specimen Type

Serum Red

Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Refrigerated (preferred) 7 days
  Frozen  30 days
  Ambient  72 hours

Clinical Information

Serum thyroglobulin (Tg) measurements are used in the follow-up of differentiated follicular cell-derived thyroid carcinoma. Because Tg is thyroid specific, serum Tg concentrations should be undetectable or very low after the thyroid gland is removed during treatment for thyroid cancer.


Most often Tg is measured by immunometric assays as they are widely available in automated high-throughput instruments, have shorter turnaround times, and have functional sensitivities of 0.1 mcg/L or less. However, these immunoassays may be affected by the presence of both anti-thyroglobulin antibody (TgAb) and heterophile antibody interferences. The presence of TgAb might cause falsely low/undetectable Tg that can mask disease; whereas heterophile antibodies might cause falsely high Tg that can be mistaken for residual or recurrent disease.


Some patients, due to exposure to animal antigens, have developed heterophile antibodies, such as human anti-mouse antibodies (HAMA), that can interfere with immunoassay testing by binding to the animal antibodies used in immunoassays. In some sandwich immunoassays, including those for Tg, the presence of heterophile antibodies in the patient’s sample might lead to a false-positive result.

Although rare, false-negative assay results due to heterophile interference have also been reported in the literature. Manufacturers often add blocking agents to their reagents, but, occasionally, patient samples containing heterophile antibodies are incompletely blocked and exhibit heterophile antibody interference. Subsequent reporting of erroneous results can have adverse effects on patient management, especially with tumor marker assays.


Dilution of the specimen prior to assay performance often yields unexpected nonlinear results in the presence of interfering substances such as heterophile antibodies and/or TgAb. Heterophile blocking tube (HBT) treatment is also utilized for troubleshooting samples that exhibit potential heterophile interference. Finally, assessment of an analyte such as Tg with an alternative assay will often lead to apparent discrepant results in the presence of heterophile antibodies and/or TgAb interference.


Measurement of Tg by liquid chromatography-tandem mass spectrometry (Tg-MS) has been introduced as a method for accurate Tg quantitation in the presence of TgAb and heterophile antibodies. Tg-MS assays are based on peptide quantitation after tryptic digestion and immunocapture of Tg-specific peptides. The advantage of trypsin digestion is that all proteins are cleaved, including both TgAb and heterophile antibodies, thus eliminating them as interferences.

Reference Values


Athyrotic: <0.1 ng/Ml

Intact thyroid: ≤33 ng/mL


Athyrotic: <0.2 ng/mL

Healthy individuals with intact, functioning thyroid: ≤33 ng/mL


<1.8 IU/mL

Reference values apply to all ages.


Specimens are evaluated for the presence of potential interfering anti-thyroglobulin (TgAb) and heterophile antibody interference in the Beckman Access thyroglobulin (Tg) immunoassay. While the presence of TgAb can result in falsely low Tg concentrations in the Beckman immunoassay, the presence of heterophile antibodies can result in falsely elevated Tg concentrations in the Beckman immunoassay. Following investigation of the presence of TgAb, heterophile antibody evaluation consists of pretreatment with commercial heterophile antibody blocking reagents, serial dilutions of the sample, and testing on an alternate platform generally unaffected by the presence of heterophile antibodies or TgAb (ie, Tg liquid chromatography-tandem mass spectrometry [Tg-MS]). The presence of heterophile antibody interference in the Beckman Access Tg immunoassay is not suspected when the results from the pretreatment, serial dilutions, and the alternative platform (Tg-MS) agree with the original result.


The presence of heterophile antibody interference in the Beckman Access Tg immunoassay is suspected when 1 or more of the following are observed: a significant decrease in Tg concentration (>20%) upon treatment of the sample with heterophile antibody blocking reagents, lack of linearity upon serial dilutions, or a significant difference in Tg concentration on the alternate platform (Tg-MS). When a heterophile antibody interference affecting the Beckman Access immunoassay is suspected, the Tg result from this assay is considered false positive and should not be used in clinical management.


Thyroglobulin Antibody:

TgAb may interfere with the measurement of Tg. TgAb should be measured in conjunction with every measurement of serum Tg to rule out potential interference. Anti-Tg antibodies greater or equal to 1.8 IU/mL are likely to cause interference in the Tg immunoassay. In the Beckman Access Tg immunoassay utilized in this interference evaluation, the presence of TgAb is most likely to cause a reduction in measured Tg concentrations. Measurement of Tg by mass spectrometry is not affected by the presence of TgAb.

Clinical Reference

1. Barbesino G, Algeciras-Schimnich A, Bornhorst JA: False positives in thyroglobulin determinations due to the presence of heterophile antibodies: an underrecognized and consequential clinical problem. Endocr Pract. 2021 May;27(5):396-400. doi: 10.1016/j.eprac.2020.10.011

2. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM,  et al: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov;19(11):1167-1214

3. Netzel BC, Grebe SKG, Algeciras-Schimnich A: Usefulness of a thyroglobulin liquid chromatography-tandem mass spectrometry assay for evaluation of suspected heterophile interference. Clin Chem. 2014 Jul;60(7):1016-1018

4. Algeciras-Schimnich A: Thyroglobulin measurement in the management of patients with differentiated thyroid cancer. Crit Rev Clin Lab Sci. 2018 May;55(3):205-218

5. Ward G, Simpson A, Boscato L, Hickman PE: The investigation of interferences in immunoassay. Clin Biochem. 2017 Dec;50(18):1306-1311

Day(s) Performed

Monday through Friday

Report Available

3 to 5 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information




LOINC Code Information

Test ID Test Order Name Order LOINC Value
IETG Interference Eval, Heterophile, TG In Process


Result ID Test Result Name Result LOINC Value
62749 Thyroglobulin, Mass Spec., S 3013-0
35998 Interpretation 59462-2
TGABI Thyroglobulin Antibody, S 56536-6
TGQN Thyroglobulin, Tumor Marker, S In Process
TGIF TG, Interference Heterophile In Process
TGIN TG, Interpretation In Process