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Thyroglobulin as a tumor marker for thyroid cancer

Thyroglobulin (Tg) is a glycoprotein created by normal follicular thyroid cells. Papillary and follicular thyroid carcinomas maintain this ability. Thyroglobulin is used as a marker for persisting disease and recurrence after a thyroidectomy. 

The level of thyroglobulin measured in serum (s-Tg) should be held under the lower measurable value when all thyroid and tumor tissue is removed.  

Thyroglobulin cannot be used as a tumor marker for work-up of a knot in the thyroid because the concentration in the blood varies with the amount of thyroid tissue, grade of TSH stimulation, pathological changes such as thyroiditis, and benign and malignant neoplasias.

Thyroglobulin production is stimulated by TSH, therefore s-Tg is measured in some contexts of exogenous or endogenous TSH stimulation to make the test more sensitive.  

s-Tg has been shown to be more sensitive than whole body scintigraphy for detection of recurrence, persisting illness, and possibly progression of persisting thyroid cancer.  

When interpreting test results, these points must be taken into consideration:

  • which primary treatment the patient has undergone
  • the TSH level at test taking
  • development of s-Tg level over time
  • whether the patient has thyroglobulin antibodies (TgAb)

Between 10-25% of the population have antibodies against Tg (TgAb). The highest incidence is seen in patients with thyroid cancer. TgAb can interfere with measurement methods for Tg. In TgAb-positive patients, TgAb will give Tg values that are too low and of limited value. Non-measureable Tg values should not be emphasized. Patients with postive TgAb must also be monitored with ultrasound of the neck and possibly whole body scintigraphy.

In patients having a raised Tg with thyroxine suppression, it is not necessary to do a stimulated Tg test before further testing.

Stimulated Tg testing

Exogenous recombinant human TSH, or possibly endogenous TSH (hypthreosis fase) increases the sensitivity of Tg testing.

It is appropriate to do endogenous or exogenous TSH stimulated Tg testing on patients with non-measurable Tg or with low Tg values (<1 µg/l in total or nearly total thyroidectomy) on thyroxine treatment.

rhTSH (Thyrogen ®)stimulated Tg testing
Day 1 Blood test before measuring Tg, Tg Ab, TSH and FT4 are taken before injection of rhTSH
Day 1 The first injection of 0.9 mg rh TSH im
Day 2 Second injection of 0.9 mg rhTSH
Day 3 Blood test for measurement of Tg, TgAb and TSH
Day 5 (72 hours) after the last injection of rhTSH, a blood test is taken to measure Tg, TgAb and TSH

Assessment of Tg values

  • Measurable Tg in total thyroidectomy patients having an ablation dose of radioative iodine indicates remaining cancer or metastasis 
  • Tg values must be assessed against the known value of remaining tissue and grade of stimulation
  • Rise of Tg values in patients on thyroxine suppression therapy is a sign of remaining cancer and/or metastases, and the patient must have further testing. 

TgAb as a prognostic factor

TgAb as a prognostic factor does not fill the prognostic requirement to be a tumor marker.  

It may be an indication of remaining tumor/recurrence/metastasis if positive TgAb is lasting, or if a TgAb-negative patient becomes positive.

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