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Thyroglobulin (Tg)

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(Thyroid-Specific Protein - Primary Tumor Marker for Differentiated Thyroid Cancer)

Synonyms

  • Thyroglobulin
  • Tg
  • Serum Tg
  • Thyroid tumor marker
  • Thyroid-specific glycoprotein
  • Thyroid follicular colloid protein

Units of Measurement

  • ng/mL
  • ng/dL
  • ng/100 mL
  • ng%
  • ng/L
  • µg/L

Unit Conversions

1 ng/mL=1 µg/L1\ \text{ng/mL} = 1\ \text{µg/L}1 ng/mL=1 µg/L 1 ng/mL=1000 ng/L1\ \text{ng/mL} = 1000\ \text{ng/L}1 ng/mL=1000 ng/L 1 ng/mL=100 ng/dL1\ \text{ng/mL} = 100\ \text{ng/dL}1 ng/mL=100 ng/dL \text{ng%} = \text{ng/dL}

Description

Thyroglobulin (Tg) is a large glycoprotein (MW ~660 kDa) produced exclusively by thyroid follicular cells, both normal and malignant.

Key Point

Because Tg is thyroid-specific, its presence after total thyroidectomy + radioiodine ablation (RAI) indicates:

  • Residual thyroid tissue
  • Recurrent disease
  • Metastatic differentiated thyroid cancer (DTC)

Tg is the primary tumor marker for:

  • Papillary thyroid carcinoma (PTC)
  • Follicular thyroid carcinoma (FTC)

Physiological Role

  • Precursor for thyroid hormone synthesis (T4, T3)
  • Stores iodinated tyrosine residues in colloid
  • Released during thyroid inflammation, manipulation, or tumor activity

Clinical Significance

HIGH THYROGLOBULIN

1. Differentiated Thyroid Cancer (DTC) - Most Important

Elevated Tg after thyroidectomy suggests:

  • Persistent disease
  • Lymph node recurrence
  • Distant metastases (lungs, bone)

ATA / NCCN Interpretation

Tg Value (suppressed)Likely Interpretation
<0.2 ng/mLExcellent response (post-thyroidectomy + RAI)
0.2 – 1 ng/mLIndeterminate
>1 ng/mLBiochemical incomplete response
>10 ng/mLStrong suspicion for recurrence
>30 ng/mLHigh risk – evaluate for structural disease

Stimulated Tg

Stimulated TgMeaning
<1 ng/mLExcellent response
>2 ng/mLSuggestive of disease
>10 ng/mLHigh probability of recurrence/metastases

2. Benign Thyroid Conditions

  • Multinodular goiter
  • Graves’ disease
  • Thyroiditis (Hashimoto, subacute)
  • Post-FNA / manipulation of the gland

Levels often increase temporarily.

3. Iodine Deficiency

Tg rises as thyroid mass increases.

4. Thyroid Injury

  • Surgery
  • RAI therapy (temporary spike)
  • Trauma

LOW / UNDETECTABLE Tg

Normal individuals with intact thyroid:

  • Tg typically 10–50 ng/mL (lab dependent)

After total thyroidectomy:

  • Undetectable Tg → excellent therapeutic response
  • Indicates absence of functioning thyroid tissue

Reference Intervals

(Tietz 8E + ATA + Mayo + ARUP)

Normal

  • Up to 50 ng/mL
    (Can vary from 1–55 ng/mL based on thyroid size and TSH levels)

Post-Thyroidectomy Targets

  • Suppressed Tg <0.2 ng/mL → Excellent response (ATA)
  • Stimulated Tg <1 ng/mL

Critical Interpretation

  • Any detectable Tg after thyroidectomy/ablation requires evaluation
  • Rising Tg trend = more important than single value

Anti-Thyroglobulin Antibodies (TgAb) - VERY IMPORTANT

TgAb interfere with Tg assays and cause falsely low or undetectable Tg.

Rules

  • ALWAYS measure TgAb with Tg
  • If TgAb positive → rely on TgAb trend, NOT Tg value
  • Rising TgAb = recurrence
  • Falling TgAb = remission

Diagnostic Uses

1. Monitoring Differentiated Thyroid Cancer

  • Postoperative surveillance
  • Detecting early recurrence
  • Monitoring metastatic disease
  • Guiding RAI therapy decisions

2. Evaluating Thyroid Tissue Remnant

Tg rises if tissue remains after surgery.

3. Thyroiditis

Elevated Tg during inflammatory destruction.

4. Iodine Deficiency Assessment

Population-based studies use Tg as marker of goiter and thyroid stress.

Analytical Notes

  • Immunometric assays (IMAs) commonly used
  • Mass spectrometry (LC–MS/MS) avoids antibody interference
  • TgAb must always be measured
  • TSH suppression status affects Tg levels
  • Avoid testing soon after:
    • FNA (up to 3 weeks)
    • Surgery
    • RAI therapy (transient spikes)

Clinical Pearls

  • Tg trend is more important than absolute value.
  • Undetectable Tg with rising TgAb = suspicious for recurrence.
  • Tg >10 ng/mL after thyroidectomy almost always indicates disease.
  • Stimulated Tg has higher sensitivity than suppressed Tg.
  • LC–MS/MS Tg is preferred when TgAb are positive.

Interesting Fact

Thyroglobulin is among the largest human proteins (≈660 kDa) and can store enough iodinated precursors to supply thyroid hormones for several weeks.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Thyroid Markers
  2. American Thyroid Association (ATA) Guidelines for Differentiated Thyroid Cancer (2015/2022)
  3. NCCN Thyroid Cancer Guidelines
  4. Mayo Clinic Laboratories - Thyroglobulin (Tg)
  5. ARUP Consult - Thyroid Tumor Markers
  6. Endocrine Society Thyroid Testing Principles

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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