Test Catalog

Test Id : HTGR

Thyroglobulin, Tumor Marker Reflex, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Reporting of accurate thyroglobulin results, depending on the antithyroglobulin antibodies status of the patient

 

Accurate measurement of serum thyroglobulin in patients with known or suspected antithyroglobulin autoantibodies or possible heterophile antibodies

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
HTGT Thyroglobulin, Tumor Marker, IA, S No No
TGMS Thyroglobulin, Mass Spec., S Yes No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test begins with the analysis of thyroglobulin antibody by immunoassay. If the thyroglobulin antibody result is negative (<1.8 IU/mL), then thyroglobulin testing will be performed by immunoassay.

 

If the thyroglobulin antibody result is positive (> or =1.8 IU/mL), then thyroglobulin testing will be performed by mass spectrometry.

Method Name
A short description of the method used to perform the test

Immunoenzymatic Assay

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Thyroglobulin Reflex to MS or IA

Aliases
Lists additional common names for a test, as an aid in searching

Anti Thyroglobulin Antibody

HTG (Human Thyroglobulin)

TG (Thyroglobulin)

Thyroglobulin Antibody

Thyroglobulin Assay for Thyroid Cancer

Thyroglobulin HTC (Human Thyro)

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test begins with the analysis of thyroglobulin antibody by immunoassay. If the thyroglobulin antibody result is negative (<1.8 IU/mL), then thyroglobulin testing will be performed by immunoassay.

 

If the thyroglobulin antibody result is positive (> or =1.8 IU/mL), then thyroglobulin testing will be performed by mass spectrometry.

Specimen Type
Describes the specimen type validated for testing

Serum Red

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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: 1 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

Useful For
Suggests clinical disorders or settings where the test may be helpful

Reporting of accurate thyroglobulin results, depending on the antithyroglobulin antibodies status of the patient

 

Accurate measurement of serum thyroglobulin in patients with known or suspected antithyroglobulin autoantibodies or possible heterophile antibodies

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test begins with the analysis of thyroglobulin antibody by immunoassay. If the thyroglobulin antibody result is negative (<1.8 IU/mL), then thyroglobulin testing will be performed by immunoassay.

 

If the thyroglobulin antibody result is positive (> or =1.8 IU/mL), then thyroglobulin testing will be performed by mass spectrometry.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Thyroglobulin (Tg) is a thyroid-specific glycoprotein (approximately 660 KDa) that serves as the source for thyroxine (T4) and triiodothyronine (T3) production within the lumen of thyroid follicles. For T4 and T3 release, Tg is reabsorbed into thyrocytes and proteolytically degraded, liberating T4 and T3 for secretion. Small amounts of intact Tg are secreted alongside T4 and T3 and are detectable in the serum of healthy individuals, with levels roughly paralleling thyroid size (0.5-1.0 ng/mL Tg per gram thyroid tissue, depending on thyroid-stimulating hormone [TSH] level). In situations of disordered thyroid growth (eg, goiter), increased thyroid activity (eg, Graves disease), or glandular destruction (eg, thyroiditis) larger amounts of Tg may be released into the circulation.

 

Clinically, the main use of serum Tg measurements is 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.

 

Current clinical guidelines consider a serum Tg of more than1 ng/mL in an athyrotic individual as suspicious of possible residual or recurrent disease. To improve diagnostic accuracy, it is recommended that this measurement be initially obtained after TSH stimulation, either following thyroid hormone withdrawal or after injection of recombinant human TSH. Most patients will have a relatively low risk of recurrence and will thereafter only require unstimulated Tg measurement. If unstimulated (on thyroxine) serum Tg measurements are less than 0.1 to 0.2 ng/mL, the risk of disease is below 1%. Patients with higher Tg levels, who have no demonstrable remnant of thyroid tissue, might require additional testing, such as further stimulated Tg measurements, neck ultrasound, or isotope imaging. A stimulated Tg above 2 ng/mL is considered suspicious.

 

The presence of anti-thyroglobulin autoantibodies (TgAb), which occur in 15% to 30% of thyroid cancer patients, could lead to misleading Tg results. In immunometric assays, the presence of TgAb can lead to false-low measurement; whereas, it might lead to false-high results in competitive assays. Traditionally, there have been no reliable means to obtain accurate Tg measurements in patients with TgAb. However, recently, trypsin digestion of serum proteins, which cuts both antibodies and Tg into predictable fragments, has allowed accurate quantification of Tg in samples with antibody interferences through measurement of Tg-specific tryptic peptides by mass spectrometry.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Thyroglobulin Antibody: <1.8 IU/mL

Interpretation
Provides information to assist in interpretation of the test results

Current guidelines recommend measurement of thyroglobulin (Tg) using a sensitive immunoassay - limit of quantification less than 1 ng/mL; for measurements of unstimulated Tg, the detection limit should be in the 0.1 to 0.2 ng/mL range.

 

In all cases, serum anti-thyroglobulin autoantibodies (TgAb) should also be measured, preferably with a method that allows detection of low concentrations of TgAb. If TgAb are detected, the laboratory report should alert the ordering provider to the possibility of false-low Tg results. If the apparent Tg concentration is less than 1.0 ng/mL, the sample should be remeasured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This will allow confident detection of Tg in the presence of TgAb down to 0.5 ng/mL (risk of residual/recurrent disease <1%-3%).

 

Samples from patients with Tg concentrations greater than 1.0 ng/mL might not require Tg measurement by mass spectrometry because current guidelines suggest further work-up might be necessary above this threshold. However, the positive predictive value for residual/recurrent disease is modest when Tg is just above this threshold (3%-25%) in athyrotic patients. Above 10 ng/mL, the risk of residual/recurrent disease is at least 25%, with many studies showing 60% to greater than 90% risks. In selected patients, it might therefore also be useful to test TgAb positive samples by mass spectrometry, even if the Tg concentration is greater than 1.0 ng/mL but has not yet passed the 10 ng/mL threshold. These considerations are even more relevant in patients with a known thyroid remnant of a few grams, who may always have serum Tg concentrations of 1.0 to 10 ng/mL, owing to remnant Tg secretion, regardless of the presence or absence of residual/recurrent cancer.

 

It has been determined that the presence of anti-thyroglobulin autoantibodies (TgAb) in serum can lead to underestimation of Tg concentration by immunometric methods. When TgAb are present in samples with detectable Tg, the Tg values may be underestimated by up to 60% in immunoassays. In addition, some specimens containing TgAb which are negative for Tg by immunoassay tested positive by LC-MS/MS. Therefore, measuring of Tg by LC-MS/MS is the preferred method in TgAb positive patients. The listed decision levels are for thyroid cancer follow-up of athyrotic patients and apply to unstimulated and stimulated thyroglobulin measurements. Decision levels are based on best practice guidelines and the literature, which includes Mayo Clinic studies.

 

Decision levels for thyroid cancer patients who are not completely athyrotic (ie, patient has some remnant normal thyroid tissue) have not been established but are likely to be somewhat higher; remnant normal thyroid tissue contributes to serum Tg concentrations 0.2 to 1.0 ng/mL per gram of remnant tissue, depending on the TSH level.

 

Thyroglobulin by Mass Spectrometry:

Tg <0.2 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Undetectable Tg levels in athyrotic individuals on suppression therapy indicate a minimal risk (<1%-2%) of clinically detectable recurrent papillary/follicular thyroid cancer.

 

Tg > or =0.2 ng/mL to 2.0 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels of 0.2-2.0 ng/mL in athyrotic individuals on suppressive therapy indicate a low risk of clinically detectable recurrent papillary/follicular thyroid cancer.

 

Tg 2.1 ng/mL to 9.9 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels of 2.1-9.9 ng/mL in athyrotic individuals on suppression therapy indicate an increased risk of clinically detectable recurrent papillary/follicular thyroid cancer.

 

Tg > or =10 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels of > or =10 ng/mL in athyrotic individuals on suppressive therapy indicate a significant (>25%) risk of clinically detectable recurrent papillary/follicular thyroid cancer.

 

Thyroglobulin by Immunoassay:

Tg <0.1 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels <0.1 ng/mL in athyrotic individuals on suppressive therapy indicate a minimal risk (<1%-2%) of clinically detectable recurrent papillary/follicular thyroid cancer.

 

Tg > or =0.1 to 2.0 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels 0.1 to 2.0 ng/mL in athyrotic individuals on suppressive therapy indicate a low risk of clinically detectable recurrent papillary/follicular thyroid cancer.

 

Tg 2.1 ng/mL to 9.9 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels 2.1 to 9.9 ng/mL in athyrotic individuals on suppressive therapy indicate an increased risk of clinically detectable recurrent papillary/follicular thyroid cancer.

 

Tg > or =10 ng/mL: Tg levels must be interpreted in the context of TSH levels, serial Tg measurements, and radioiodine ablation status. Tg levels > or =10 ng/mL in athyrotic individuals on suppressive therapy indicate a significant risk (>25%) of clinically detectable recurrent papillary/follicular thyroid cancer.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Thyroglobulin Antibody:

Antithyroglobulin values determined by different methodologies might vary significantly and cannot be directly compared with one another. Some patients might be antibody-positive by some methods and antibody-negative by others. Comparing values from different methods might lead to erroneous clinical interpretation.

 

Thyroglobulin by Mass Spectrometry:

Rare normal amino acid sequence variations within thyroglobulin (Tg) can cause a false-low result in the Tg mass spectrometry assay if they happen to be present in the Tg proteotypic peptides that are used for Tg quantification.


While the exact prevalence of such changes is unknown, the validation data on large sample numbers indicate that this affects less than 1% of samples. In the heterozygote state, the result would be an apparent reduction in Tg concentration by about 50%, while the homozygous state (<0.01%) is predicted to result in total loss of signal. Therefore, if the results of the mass spectrometry measurement are much lower than those obtained previously (within 3-6 months) with an immunometric immunoassay, this possibility should be considered. In this event, alert Mayo Clinic Laboratories as soon as possible, and an attempt will be made to resolve the discrepancy.

 

Thyroglobulin by Immunoassay:

Thyroid autoantibodies may interfere with the measurement of Tg by immunometric methods leading to an underestimation of the Tg present. Heterophile antibodies may also interfere. Specimens with thyroglobulin concentrations greater than 250,000 ng/mL may "hook" and appear to have markedly lower levels when assayed by immunoassay.

 

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies or heterophile antibodies), which may cause interference in some immunoassays. Caution should be used in interpretation of results and the laboratory should be alerted if the result does not correlate with the clinical presentation.

Supportive Data

 

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Grebe SKG: Diagnosis and management of thyroid carcinoma: A focus on serum thyroglobulin. Expert Rev Endocrinol Metab. 2009;4(1):25-43. doi: 10.1586/17446651.4.1.25

2. Cooper DS, Doherty GM, Haugen BR, et al: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov;19(11):1167-1214. doi: 10.1089/thy.2009.0110

3. Pacini F, Catagana MG, Brilli L, Pentheroudakis G, on behalf of the ESMO Guidelines Working Group: Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010 May;21 Suppl 5:v214-9. doi: 10.1093/annonc/mdq190

4. National Comprehensive Cancer Network (NCCN) guidelines for treatment of cancer by site: version 2.2022: Thyroid Carcinoma. Accessed June 7, 2022. Available at www.nccn.org/professionals/physician_gls/default.aspx#site

5. Tuttle RM: Differentiated thyroid cancer: Role of serum thyroglobulin In: Cooper DS, Ross DS, Mulder JE, eds UpToDate. Updated July 15, 2021. Accessed June 7, 2022. Available at: www.uptodate.com/contents/differentiated-thyroid-cancer-role-of-serum-thyroglobulin

Method Description
Describes how the test is performed and provides a method-specific reference

The Access Thyroglobulin Antibody II assay (TgAb) is a sequential 2-step immunoenzymatic (sandwich) assay, performed on a Beckman Coulter Unicel DxI 800 system. A sample is added to a reaction vessel with paramagnetic particles coated with the thyroglobulin protein. The serum TgAb binds to the thyroglobulin. After incubation in a reaction vessel, materials bound to the solid phase are held in place by a magnetic field, while unbound materials are washed away. The thyroglobulin-alkaline phosphatase conjugate is added and binds to the TgAb. After the second incubation, materials bound to the solid phase are held in place by a magnetic field, while unbound materials are washed away. Then, the chemiluminescent substrate, Lumi-Phos 530 is added to the reaction vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of thyroglobulin antibody in the sample.(Instruction Manual: Thyroglobulin Antibody II Assay. Beckman Coulter, Inc; 2011)

 

Thyroglobulin by immunoassay is performed using a Beckman Coulter Unicel DxI 800 system. The Access Thyroglobulin (Tg) assay is a simultaneous 1-step immunoenzymatic (sandwich) assay. A sample is added to a reaction vessel, along with a biotinylated mixture of 4 monoclonal anti-Tg antibodies, streptavidin-coated paramagnetic particles, and monoclonal anti-Tg antibody alkaline phosphatase conjugate. The biotinylated antibodies and the serum Tg binds to the solid phase, while the conjugate antibody reacts with a different antigenic site on the Tg molecule. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate Lumi-Phos 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of Tg in the sample.(Instruction manual: Beckman Coulter Assay Manual. Beckamn-Coulter, Inc; 2010)

 

Thyroglobulin by mass spectrometry is performed as follows: serum is fractionated by a salting out method. Fractionated serum is then reduced, alkylated, and digested with trypsin. Tryptic fragments are further purified by immunocapture with antibodies specific to the individual fragments. Finally, these fragments are analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

TGABR, HTGT: Monday through Saturday

TGMS: Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

12 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

86800

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
HTGR Thyroglobulin Reflex to MS or IA 56536-6
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
TGABR Thyroglobulin Antibody, S 56536-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
Test Status - Test Resumed 2022-08-10
Test Status - Test Delay 2022-07-29
Test Status - Test Delay 2022-07-29