Test Catalog

Test Id : TGMS

Thyroglobulin Mass Spectrometry, Serum

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

Accurate measurement of serum thyroglobulin (Tg) in patients with known or suspected antithyroglobulin autoantibodies (TgAb) or heterophile antibodies (HAb)

 

Reflex testing of samples with previously unknown TgAb status that prove TgAb positive during immunoassay testing

 

Assisting in the differential diagnosis of early phase silent thyroiditis versus Graves' disease in patients without thyroid cancer (the mass spectrometry-based method would only be required if these patients have TgAb or HAb)

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

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)

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, Mass Spec., S

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

HTG (Human Thyroglobulin)

TATC (Thyroglobulin Assay for Thyroid Cancer)

TG (Thyroglobulin)

Thyroglobulin Assay for Thyroid Cancer

Thyroglobulin HTC (Human Thyro)

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

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

Specimen Volume: 1.25 mL

Forms

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

0.75 mL

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

Gross hemolysis Reject
Gross lipemia OK
Gross icterus 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 416 days
Ambient 72 hours

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

Accurate measurement of serum thyroglobulin (Tg) in patients with known or suspected antithyroglobulin autoantibodies (TgAb) or heterophile antibodies (HAb)

 

Reflex testing of samples with previously unknown TgAb status that prove TgAb positive during immunoassay testing

 

Assisting in the differential diagnosis of early phase silent thyroiditis versus Graves' disease in patients without thyroid cancer (the mass spectrometry-based method would only be required if these patients have TgAb or HAb)

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

Thyroglobulin (Tg) is a highly thyroid-specific large homodimeric glycoprotein (approximately 660 KDa). It contains 8% to 10% of carbohydrates and iodine. Thyroxine (T4) and triiodothyronine (T3) are synthesized on Tg 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 highly organ-specific, serum Tg concentrations should be undetectable, or very low, after the thyroid gland is removed during primary treatment for thyroid cancer.

 

Current clinical guidelines consider a serum Tg of more than 1 ng/mL in an athyrotic individual as suspicious of possible residual or recurrent disease. To improve diagnostic accuracy, it is recommended that at least initially this measurement is 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.

 

There are 3 situations, when serum Tg measurement might be misleading:

1. Remnant thyroid tissue (see above, 0.5-1 ng/mL Tg per gram)

2. Antithyroglobulin autoantibodies (TgAb), which occur in 15% to 30% of thyroid cancer patients, can lead to false-low measurement in immunometric assays (most commonly used); in competitive assays they may cause false-high results.

3. Heterophile antibodies (HAb) are antibodies that are capable of interacting with the antibodies used in immunoassays, usually resulting in false-high measurements. Depending on the assay and the patient population, this can lead to erroneously high results in 0.1% to 3.0% of patients.

 

Traditionally, there have been no reliable means to obtain accurate Tg measurements in patients with TgAb or HAb. 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.

Healthy individuals with intact, functioning thyroid: < or =33 ng/mL

The reference ranges listed below, however, are for thyroid cancer follow up of athyrotic patients and apply to unstimulated and stimulated thyroglobulin (Tg) measurements. Ranges are based on best practice guidelines and the literature, which includes Mayo Clinic studies, and represent clinical decision levels.

 

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 0.2-1.0 ng/mL per gram of remnant tissue, depending on the thyroid-stimulating hormone (TSH) level.

 

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 10 ng/mL or above in athyrotic individuals on suppressive therapy indicate a significant (>25%) risk of clinically detectable recurrent papillary/follicular thyroid cancer.

Interpretation
Provides information to assist in interpretation of the test results

Current guidelines recommend measurement of thyroglobulin (Tg) with a sensitive immunoassay limit of quantification below 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 antithyroglobulin autoantibodies (TgAb) should also be measured, preferably with a method that allows detection of low concentrations of TgAB (< or =20 kIU/L). 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 below 1 ng/mL, the sample should be remeasured by mass spectrometry. This will allow confident detection of Tg in the presence of TgAb down to 0.2 ng/mL (risk of residual/recurrent disease <1-3%).

 

Samples from patients with Tg concentrations above 1 ng/mL (or 2 ng/mL; there is some discussion in the literature) 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 at best when Tg is just above this threshold (3%-25%, rising in parallel with Tg concentrations up to 10 ng/mL) in athyrotic patients. Above 10 ng/mL, the risk of residual/recurrent disease is at least 25%, with many studies showing 60% to >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 above 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 between 1.0 and 10 ng/mL, owing to remnant Tg secretion, regardless of the presence or absence of residual/recurrent cancer.

 

There are no routine tests that can detect heterophile antibodies in patient samples. An unexpected high result is usually the tip-off in this case and should prompt remeasurement by mass spectrometry, which will provide a reliable result.

 

It has been determined that the presence of TgAb in serum can lead to underestimation of Tg concentration by immunoassay methods. When antibodies are present in samples with detectable Tg, the Tg values may be underestimated by up to 60% in immunoassays. In addition, 20% of specimens containing antibodies that are negative for Tg by immunoassay tested positive by liquid chromatography-tandem mass spectrometry (LC-MS/MS); no results over 3 ng/mL by LC-MS/MS were observed.

 

In rare cases, when Tg is measured in patients with an intact thyroid gland who do not have thyroid cancer, substantial elevations will primarily be observed in very large goiters, highly active Graves disease, and, most pronounced, in the early phase of acute thyroiditis when follicular destruction releases massive amounts of stored Tg into the circulation. Levels are often well above 100 ng/mL.

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

The test is most sensitive for detection of thyroid cancer recurrence when patients are off thyroid replacement long enough to have an elevated thyroid-stimulating hormone (TSH) prior to collecting the specimen. This test also can be used to follow patients with normal TSH; however, thyroglobulin (Tg) values from specimens with high TSH should not be compared with values with normal TSH, because TSH stimulation may change the baseline determinations, if any residual benign thyroid tissue is still present.

 

Rare normal amino acid sequence variations within 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, 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, the recommend is to alert the lab as soon as possible, and they will attempt to resolve the discrepancy.

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. Exp Rev Endocrinol Metab 2009;4:25-43

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;19:1167-1214

3. Pacini F, Catagana MG, Brilli L, Pehteroudakis G, on behalf of the ESMO Guidelines Working Group: Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(Supplement 5):v214-v219

4. National Comprehensive Cancer Network (NCCN) guidelines for treatment of cancer by site: version 2.2013: Thyroid Carcinoma. Accessed April 2020 Available at www.nccn.org/professionals/physician_gls/default.aspx#site

5. Tuttle, RM: Serum thyroglobulin in the management of differentiated thyroid cancer. Updated June 2019. Accessed April 2020. Available at www.uptodate.com/contents/differentiated-thyroid-cancer-role-of-serum-thyroglobulin/print

6. Haugen BR, Alexander EK, Bible KC, et al: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016;26(1):1-133 doi:10.1089/thy.2015.0020

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

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.

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.

3 to 5 days

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

14 months

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

Rochester

Fees
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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 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
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.

84432

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
TGMS Thyroglobulin, Mass Spec., S 3013-0
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.
62749 Thyroglobulin, Mass Spec., S 3013-0
35998 Interpretation 59462-2

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