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Tumor Markers:- Part 10 – Thyroglobulin (Tg) as Tumor marker

January 4, 2025Chemical pathologyLab Tests

Table of Contents

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  • Thyroglobulin (Tg)
        • What sample is needed for Thyroglobulin (Tg)?
        • What are the Indications for Thyroglobulin (Tg)?
        • What precautions are needed to estimate thyroglobulin (Tg)?
        • How will you discuss the pathophysiology of Thyroglobulin (Tg)?
        • What is the difference between thyroglobulin and thyroxine-binding globulin?
        • Does Thyroglobulin call a tumor marker?
        • What are the advantages of thyroglobulin in cancer patients?
        • How will you discuss the Thyrogen-stimulation test?
        • What is the importance of the presence of antithyroglobulin antibodies?
        • What are the normal Thyroglobulin (Tg) values?
          • Male Thyroglobulin (Tg)
        • What are the causes of increased Thyroglobulin (Tg) levels?
        • What are the causes of decreased Thyroglobulin (Tg) levels?
      • Questions and answers:

Thyroglobulin (Tg)

What sample is needed for Thyroglobulin (Tg)?

  • Venous blood is needed to prepare the serum.

What are the Indications for Thyroglobulin (Tg)?

  1. Thyroglobulin is advised after the treatment of thyroid cancer.
  2. It is advised to assess the presence and possibly extent of residual, recurrent, or metastatic follicular or papillary carcinoma.
  3. This is done to diagnose hyperthyroidism.
  4. This is the tumor marker for well-differentiated thyroid cancer (follicular and papillary).
    1. Thyroglobulin is not elaborated by medullary or anaplastic thyroid cancer.
  5. This can also help to monitor thyroid cancer or metastatic cancer.
  6. It predicts the outcome of therapy for hyperthyroidism.
  7. The presence of pleural effusion indicates metastatic differentiated thyroid carcinoma.

What precautions are needed to estimate thyroglobulin (Tg)?

  1. Make sure that patients are off the thyroid medication for 6 weeks.
  2. Evaluate the TSH level before testing the Tg.
  3. Anti-Tg antibodies are present in 15% to 35% of patients with thyroid cancer. These will interfere with the Tg results.
  4. It is not recommended for initial diagnosis of thyroid carcinoma.
  5. Do not use in patients with preexisting thyroid diseases.

How will you discuss the pathophysiology of Thyroglobulin (Tg)?

  1. Definition of thyroglobulin:
    1. It is an iodine-containing glycoprotein of high molecular weight (660 kD) that is present in the colloid of the thyroid follicles.
  2. It is synthesized and secreted by the thyroid follicles. Up to 30 ng/mL (45 pmol/L) of it is present in the serum of normal people.
    1. Thyroglobulin (Tg) represents the thyroid mass.
  3. Thyroglobulin is a glycoprotein, 660 kD, and iodinated secretion of epithelial cells of the thyroid gland.
    1. It is synthesized and secreted by the thyroid follicular cells.
Thyroglobulin (Tg)

Thyroglobulin (Tg)

Thyroglobulin role in T3 T4 synthesis

Thyroglobulin Role in T3 T4 Synthesis

  1. Thyroglobulin is a precursor of the thyroid hormone.
  2. This may be made by normal epithelial cells and cancer cells.
  3. Raised values of thyroglobulin (Tg) are found in the following:
    1. Thyrotoxicosis.
    2. Thyroiditis.
    3. Iodine deficiency.
    4. Benign thyroid adenomas.
    5. Differentiated thyroid carcinomas (follicular and papillary carcinoma and papillary-follicular carcinoma).
      1. Medullary carcinoma does not produce thyroglobulin (Tg).
  4. A very low level of Tg after thyroid surgery indicates that there is little left in the thyroid tissues.
  5. In the case of functional carcinoma, thyroglobulin should not be detected after thyroidectomy or radioiodine uptake.
    1. Thyroglobulin is detected in case of incomplete surgery.
  6. The iodinated secretion also contains T3, T4, and hormones.

What is the difference between thyroglobulin and thyroxine-binding globulin?

Clinical parameter Thyroglobulin (Tg) Thyroxine-Binding Globulin (TBG)
  • Primary role
  • Precursor for T3/T4 synthesis
  • Transport of T3 and T4 in the blood
  • Site of formation
  • Thyroid gland (Follicular epithelial cells)
  • It is synthesized in the liver
  • Importance
  • Used as a Tumor marker for cancers
  • Assessment of hormone binding anomalies
  • Location
  • Stored in the thyroid gland
  • Circulates in the bloodstream
  • Both proteins are essential for proper thyroid function, but their roles are distinct—one is involved in hormone production (Tg), and the other in hormone transport (TBG).

Does Thyroglobulin call a tumor marker?

  1. Half-life is about 65 hours (another reference days 8 to 22 hours).
  2. It takes nearly a month before thyroglobulin becomes undetectable following total thyroidectomy.
  3. In cancer cases operated on, Thyroglobulin (Tg) is measured postoperatively to determine the disease’s activity and the volume of thyroid tissue left behind.
  4. The rising level of Thyroglobulin (Tg) indicates tumor recurrence and progression.
    1. Thyroglobulin (Tg) is also raised in benign conditions, so it is not specific or sensitive enough to diagnose thyroid cancer.
  5. After thyroidectomy, thyroid hormone replacement is needed for normal body metabolism.
    1. Because of thyroid hormone replacement, TSH levels are low, so there is minimal stimulation of thyroid cells.
    2. To stimulate Thyroglobulin (Tg) in thyroid cancer cases after thyroidectomy, stop the hormone replacement for at least 6 weeks.
      1. Now, TSH will be stimulated, stimulating Thyroglobulin (Tg) production from the epithelial cells.
      2. If there are any leftover thyroid cancer cells, the Thyroglobulin (Tg) level will increase.
      3. After surgery and radiation in cancer patients,  the Thyroglobulin (Tg) level is undetectable.
Thyroglobulin in cancer cases

Thyroglobulin in cancer cases

What are the advantages of thyroglobulin in cancer patients?

  1. A thyroid tumor scan with I131 is required to differentiate begin and cancer cells.
  2. Thyroglobulin estimation advantage is less exposure to radiation in the form of I131.
  3. With thyroglobulin estimation, I131 is not needed.
  4. Patients with metastasis are not detected by the I131 scan, where thyroglobulin (Tg) is raised.

How will you discuss the Thyrogen-stimulation test?

  1. Thyrogen is a synthetic purified recombinant source like a human thyroid-stimulating hormone (TSH).
  2. Thyrogen is synthetic TSH and is called thyrotropin alpha.
  3. Keep the patient off the hormone replacement therapy.
  4. Two injections of thyrogen are given on two consecutive days.
  5. Take a blood sample of the patient for thyroid hormones and thyroglobulin.
  6. Normal thyroid tissue and thyroid cancer cells raise >10 times Tg level by TSH stimulation.
    1. Thyrogen stimulates the thyroid gland and raises the thyroglobulin (Tg) level.
  7. What are the advantages of the thyrogen test?
    1. It monitors patients who have undergone thyroid surgery.
    2. It can detect residual tumors.
    3. It helps to determine the proper dosage of hormone replacement therapy.

What is the importance of the presence of antithyroglobulin antibodies?

  1. Anti-thyroglobulin antibodies are present in 10% of the normal population and 20% of those with thyroid cancer and are a major issue in thyroglobulin testing.

What are the normal Thyroglobulin (Tg) values?

Source 1

Age ng/mL
Cord blood 24.4 ± 3.7
One hour 29.7 ± 4.2
48 hours 41.9 ± 5.8
Adult 3 to 42
Thyroid patient <5
  • To convert into SI unit x 1.0 = µg/L
Male Thyroglobulin (Tg)
  • 0 to 11 months = 0.6 to 5.5 ng/mL.
  • 1 to 11 years = 0.6 to 50.1 ng/mL.
  • Adult = 0.5 to 53 ng/mL.

Female Thyroglobulin (Tg)

  • 1 to 11 months = 0.5 to 5.5 ng/mL.
  • 1 to 11 years = 0.5 to 52.1 ng/mL.
  • Adult = 0.5 to 43 ng/mL.
  • Another source gives normal values as follows:
    • Adult = 3 to 42 ng/mL.
    • Newborn = 36 to 48 ng/mL.
    • 87% of normal adults have a serum value of <10 ng/mL.

What are the causes of increased Thyroglobulin (Tg) levels?

  1. Thyroid follicular and papillary carcinoma.
  2. Thyroid adenoma.
  3. Untreated and metastatic thyroid cancer.
  4. Subacute thyroiditis, Hashimoto’s thyroiditis, and Grave’s disease.
  5. Benign thyroid adenoma.
  6. Hypothyroidism.
  7. Recurrence of the metastatic tumor after the treatment.
  8. Some patients with endemic goiter.
  9. Silent, painless thyroiditis.
  10. Marked liver insufficiency.

What are the causes of decreased Thyroglobulin (Tg) levels?

  1. Infants with goiter (Hypothyroidism).
  2. Thyrotoxicosis factitia.
  3. Thyroid agenesis in infants.
  4. Total thyroidectomy with radiation.

Questions and answers:

Question 1: What is thyrogen test?
Show answer
Thyrogen is synthetic TSH which stimulates the remnant of the thyroid tissue after the thyroid cancer surgery.
Question 2: What is the site of formation of thyroglobulin?
Show answer
Thyroglobulin is formed by the follicular epithelial cells.

Possible References Used
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