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

Sample

• Venous blood needed to prepare the serum.

Purpose of the test (Indications)

1. This is done to diagnose hyperthyroidism.
2. This is the tumor marker for well-differentiated thyroid cancer (follicular and papillary).
3. Thyroglobulin is not elaborated by medullary or anaplastic thyroid cancer.
4. This can also help to monitor thyroid cancer or metastatic cancer.

Precautions

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.

Pathophysiology

1. Thyroglobulin is a glycoprotein, 660kD, and iodinated secretion of epithelial cells of the thyroid gland.
   1. It is synthesized and secreted by the thyroid follicular cells.

2. Thyroglobulin is a precursor of the thyroid hormone.
3. This may be made by normal epithelial cells and as well as by the cancer cells.
4. If there is a very low level of Tg after the surgery of thyroid indicates very little leftover of the thyroid tissues.
5. The iodinated secretion also contains T3, T4, and hormones.

6. Tg is also called as a tumor marker.
   1. Half-life is about 65 hours. It takes a nearly month before thyroglobulin becomes undetectable following total thyroidectomy.
   2. In the operated cases of cancer, Tg postoperatively gives the idea about the activity of the disease and the volume of thyroid tissue left behind.
   3. The rising level of Tg indicates tumor recurrence and progression.
   4. Tg is also raised in benign conditions as well, so not specific or sensitive for the diagnosis of thyroid cancer.
7. After thyroidectomy, thyroid hormone replacement is needed for normal body metabolism.
   1. Because of thyroid hormone replacement TSH level is low, so minimal stimulation of thyroid cells.
   2. To stimulate Tg in thyroid cancer cases after thyroidectomy, stop the hormone replacement for at least 6 weeks.
      1. Now TSH will be stimulated and this will stimulate Tg production form the epithelial cells.
      2. If there is any leftover of the thyroid cancer cells then the Tg level will increase.
      3. After surgery and radiation of cancer patients,  the Tg level is undetectable.

6. Depletion of hormones is needed because of the Thyrogen-stimulation test.
   1. Thyrogen is a synthetic purified recombinant source like a human thyroid-stimulating hormone (TSH).
   2. Thyrogen stimulates the thyroid and will raise the Tg level.
      1. Normal thyroid tissue and thyroid cancer cells raise  >10 times Tg level by TSH stimulation.
      2. By the hydrogen stimulation test, the thyroglobulin (Tg) level will be detectable.
7. 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.

Normal

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

• 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

• 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 the normal adults have a serum value of <10 ng/mL.

Increased thyroglobulin level is seen in:

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.

Decreased Thyroglobulin level is seen in:

1. Infants with goiter (Hypothyroidism).
2. Thyrotoxicosis factitia.

---