thyroglobulin and recurent thyroid cancer

Last edited 12/2022 and last reviewed 02/2023

  • serum thyroglobulin (Tg) is a reliable marker for detecting recurrent and persistent disease during the follow-up of patients with papillary and follicular thyroid carcinoma.
  • thyroglobulin is a specific tumour marker after differentiated thyroid cancer (DTC) patients have undergone total thyroidectomy and ablative therapy with radioactive iodine. The test is based upon the assumption that Tg levels must be undetectable in the absence of neoplastic or normal thyroid tissue. However, serum Tg levels are strictly dependent on TSH stimulation: when TSH is suppressed by thyroid hormone suppressive therapy (THST) administration (as generally occurs in DTC patients) serum Tg may be undetectable in as many as 20% of patients with persistent disease (1)
    • serum Tg measurements under TSH stimulation are therefore required, which are usually obtained by THST withdrawal for 4-5 weeks with the consequent endogenous TSH rise. However the availability of rhTSH permits stimulation of Tg without THST withdrawal, thus avoiding severe hypothyroidism and its adverse effects
      • however that in DTC patients with persistent disease and low Tg levels, optimization of the diagnostic use of Tg measurement after rhTSH may require rhTSH dose adjustment to the patient body surface area and repeated blood sampling, in order to improve diagnostic accuracy (1)

Note also that persistently elevated thyroglobulin antiboidies (TgAb) levels also appear to serve as a useful marker for recurrent or persistent DTC in patients with undetectable serum Tg results. Thus, the routine measurement of TgAb in such patient populations may be indicated (2)

NICE state (3):

Post-thyroidectomy monitoring of differentiated thyroid cancer

Measuring thyroglobulin and thyroglobulin antibodies

Clinicians must be aware that:

  • presence of thyroglobulin antibodies, above the laboratory threshold, can interfere with the measurement of thyroglobulin levels
  • detectable thyroglobulin levels in people without thyroglobulin antibodies suggest the presence of either residual thyroid tissue or residual or recurrent thyroid cancer.

Thyroglobulin measurement should be offered alongside measurement of thyroglobulin antibodies in people with differentiated thyroid cancer who have had total or completion thyroidectomy and radioactive iodine (RAI). Measure at:

  • 3- to 6-month intervals in the first 2 years after RAI ablation and
  • 6- to 12-month intervals thereafter

Further investigations should be considered if a person has had total thyroidectomy and RAI, and:

  • has detectable thyroglobulin levels without thyroglobulin antibodies
  • investigations have not shown recurrent or residual cancer in the presence of detectable thyroglobulin without thyroglobulin antibodies, and now the thyroglobulin levels without thyroglobulin antibodies are rising

Further investigations should be considered if a person has had a total thyroidectomy without RAI and has rising thyroglobulin levels without thyroglobulin antibodies.

Further investigation should be considered when thyroglobulin antibodies are first detected above the laboratory threshold or at any point if the levels of thyroglobulin or thyroglobulin antibodies are rising

Consider either a stimulated thyroglobulin test or highly sensitive thyroglobulin test if thyroglobulin is undetectable on a standard assay in people who have had a total or completion thyroidectomy and RAI, and have no evidence of structural persistent disease

Reference:

  1. Clin Endocrinol (Oxf). 2003 May;58(5):556-61.
  2. Clin Endocrinol (Oxf). 2002 Aug;57(2):215-21.
  3. NICE (December 2022). Thyroid cancer: assessment and management