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Test ID HTG2 Thyroglobulin, Tumor Marker, Serum

Useful For

Follow-up of patients with differentiated thyroid cancers after thyroidectomy and radioactive iodine ablation

Testing Algorithm

All specimens are screened for the presence of autoantibodies to thyroglobulin.

Reporting Name

Thyroglobulin, Tumor Marker

Specimen Type

Serum Red


Specimen Required


Patient Preparation: Twelve hours before this test, do not take multivitamins or dietary supplements containing biotin or vitamin B7 that are commonly found in hair, skin and nail supplements and multivitamins.

Collection Container/Tube: Red top

Submission Container/Tube: Plastic screw-top aliquot tube

Specimen Volume: 1 mL

Collection Instructions: Red-top tubes should be centrifuged and aliquoted within 2 hours of collection.


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

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

Clinical Information

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, Grave 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 >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 <0.1 to 0.2 ng/mL, the risk of disease is <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 >2 ng/mL is considered suspicious. The presence of antithyroglobulin 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 results; 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- by mass spectrometry. Refer to TGMS / Thyroglobulin Mass Spectrometry, Serum for accurate sample analysis of patients who are known to be TgAb positive. If TgAb status is unknown, refer to HTGR / Thyroglobulin, Tumor Marker Reflex to LC-MS/MS or Immunoassay. When HTGR is ordered, TgAb testing is performed first. If TgAb is negative (<4.0 IU/mL), Tg is assayed by immunoassay (sensitive down to 0.1 ng/mL). If TgAb is positive, Tg is assayed by mass spectrometry (sensitive down to 0.5 ng/mL).

Reference Values

THYROGLOBULIN, TUMOR MARKER

Athyrotic: <0.1 ng/mL

Intact thyroid ≤33 ng/mL

THYROGLOBULIN ANTIBODY

< 4.0 IU/mL

Reference values apply to all ages.

Interpretation

Current guidelines recommend measurement of thyroglobulin (Tg) with a sensitive immunoassay (limit of quantification <1.0 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 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 using an immunometric assay. If the apparent Tg concentration is <1.0 ng/mL, the sample should be remeasured by mass spectrometry. This will allow accurate 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 >1.0 ng/mL might not require Tg measurement by mass spectrometry, because current guidelines suggest further workup 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 >90% risks. In selected patients, therefore, it might also be useful to test TgAb positive samples by mass spectrometry, even if the Tg concentration is >1.0 ng/mL, but not above 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 antithyroglobulin 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, approximately 20% of specimens containing TgAb, which are negative for Tg by immunoassay, tested positive by LC-MS/MS. Therefore, measuring of Tg by mass spectrometry is the preferred method in TgAb positive patients.

 

The decision levels listed below, 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 0.5 to 1.0 ng/mL per gram of remnant tissue, depending on the thyroid-stimulating hormone (TSH) level.

 

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

Clinical Reference

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. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Taskforce. Thyroid 2009;19:1167-1214

3. Pacini F, Catagana MG, Brilli L, et al: 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 June 2014 Available at http://www.nccn.org

5. Tuttle, RM: Serum thyroglobulin in the management of differentiated thyroid cancer. Accessed June 2014 Available at http://www.update.com

Day(s) and Time(s) Performed

Monday through Friday 6 a.m. - 12 a.m., Saturday 6 a.m. - 6 p.m.

Analytic Time

Same day/1 day

Test Classification

This test has been cleared or approved by the U.S. 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

84432-Thyroglobulin, tumor marker

86800-Thyroglobulin antibody screen

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HTG2 Thyroglobulin, Tumor Marker 57780-9

 

Result ID Test Result Name Result LOINC Value
TGAB2 Thyroglobulin Antibody, S 56536-6
HTGN2 Thyroglobulin, Tumor Marker, S 3013-0
HTG2I Thyroglobulin Interpretation 69053-7

Method Name

Immunoenzymatic Assay

Forms

If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

General Request Form (T239) (http://www.mayomedicallaboratories.com/it-mmfiles/general-request-form.pdf)

Oncology Test Request Form (T729) (http://www.mayomedicallaboratories.com/it-mmfiles/oncology-request-form.pdf)