- Thyroglobulin (Tg):
- Is a large glycoprotein that is stored as colloid:
- The primary storage form of thyroid hormone, in the lumen of thyroid follicles
- It is continuously secreted into circulation from the thyroid gland:
- Thereby reflecting the mass of normal and malignant thyroid tissue
- Is a large glycoprotein that is stored as colloid:
- Higher serum concentrations result from:
- TSH stimulation and / or injury of thyroid tissue:
- However, for the individual with an intact thyroid gland:
- Its clinical value for evaluating thyroid dysfunction or goiter is limited in the era of modern serum thyroid function testing and imaging
- However, the demonstration of a suppressed serum Tg level in such a patient can be useful in differentiating factitious thyrotoxicosis (from exogenous thyroid hormone ingestion) from excessive endogenous thyroid hormone release of any etiology:
- In this situation, when thyrotoxicosis is due to ingestion of exogenous thyroid hormone:
- Normal thyroid hormone production is suppressed and serum Tg levels are decreased
- In contrast, if excess thyroid hormone is produced from the thyroid:
- Serum Tg levels are elevated
- In this situation, when thyrotoxicosis is due to ingestion of exogenous thyroid hormone:
- However, for the individual with an intact thyroid gland:
- TSH stimulation and / or injury of thyroid tissue:
- In current clinical practice:
- The primary use of serum Tg concentrations is as a tumor marker in patients with differentiated thyroid cancer:
- That is obtained to detect persistent and / or recurrent disease after a total thyroidectomy and radioactive iodine (131I) ablation
- The primary use of serum Tg concentrations is as a tumor marker in patients with differentiated thyroid cancer:
- Most Tg assays have only first-generation functional sensitivity between 0.5 and 1 ng/mL:
- But the second generation Tg assays are rapidly becoming the standard and have an improved functional sensitivity of 0.05 to 0.1 ng/mL
- The Tg assay can be made more sensitive to detect persistent or recurrent tumor:
- After stimulation by TSH:
- Either endogenously by withholding thyroxine treatment in an athyreotic patient or with administration of recombinant human TSH (rhTSH):
- The latter of which results in an approximate tenfold increase in basal serum Tg concentrations
- Either endogenously by withholding thyroxine treatment in an athyreotic patient or with administration of recombinant human TSH (rhTSH):
- After stimulation by TSH:
- Detection of persistent and / or recurrent disease in thyroid cancer depends on the performance of Tg immunometric assays:
- Which currently have suboptimal sensitivity and high interassay variability
- Virtually all immunometric methods:
- Will report an undetectable Tg level in euthyroid Tg Ab positive controls:
- Approximately 25% of patients with differentiated thyroid cancer have a positive serum TgAb titer:
- Thus when a suspicious lymph node or neck mass is detected in an individual who has undergone a total thyroidectomy:
- An unmeasurable basal or rhTSH-stimulated Tg in the setting of a positive serum TgAb level:
- Does not necessarily exclude thyroid cancer recurrence
- An unmeasurable basal or rhTSH-stimulated Tg in the setting of a positive serum TgAb level:
- It is reasonable in this relatively uncommon situation to measure Tg instead by Tg Ab-resistant radioimmunoassay (RIA) or liquid chromatography tandem mass spectrometry:
- Which are available at some specialty endocrine laboratories.
- Thus when a suspicious lymph node or neck mass is detected in an individual who has undergone a total thyroidectomy:
- Approximately 25% of patients with differentiated thyroid cancer have a positive serum TgAb titer:
- Will report an undetectable Tg level in euthyroid Tg Ab positive controls:
- When the serum Tg Ab titer is positive:
- It may also be used as a surrogate marker of tumor persistence / recurrence
- In one study, a > 50% decrease of Tg Ab levels within the first year after a total thyroidectomy:
- Was associated with the absence of tumor recurrence / persistence in all patients studied
- Tumor recurrence / persistence was present in 37% of patients who had any rise of serum Tg Ab within the same period
- Thus thyroid cancer patients with rising Tg antibody levels:
- Are at high risk for disease persistence / recurrence and should be evaluated promptly
- In addition, the sensitivities and absolute values reported by different methods of measuring Tg and TgAb are highly variable:
- It is essential to always use the same Tg and TgAb method when following an individual over time for tumor persistence/recurrence
- Finally, the presence of interfering heterophile antibodies (antibodies against the animal-derived antibodies used in the immunometric assay):
- May rarely result in abnormally high or low serum Tg levels
- The most common interfering antibodies are HAMAs:
- Clinically, this should be suspected when an elevated serum Tg level is inappropriate for the clinical situation and does not increase with rhTSH stimulation
- When heterophile antibody is suspected, the clinician should repeat the test using a commercially available heterophile-blocking tube (HBT) or measure Tg with an RIA assay
Rodrigo Arrangoiz MS, MD, FACS, FSSO 