What are the differences between thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb), and when should each be ordered?

Thyroglobulin Antibody vs. Thyroid Peroxidase Antibody: Key Differences and Clinical Use

TPO antibodies (TPOAb) are the superior and most predictive marker for autoimmune thyroid disease and progression to hypothyroidism, and should be the primary antibody ordered in most clinical scenarios. 1, 2

Predictive Value and Clinical Significance

TPOAb is the strongest predictor of progression to hypothyroidism in multivariate analysis, conferring a 4.3% annual risk of developing overt hypothyroidism in antibody-positive individuals versus 2.6% per year in antibody-negative patients. 1, 3 In contrast, TgAb is inferior to TPOAb for predicting thyroid dysfunction. 4, 1

Key Mechanistic Differences

• TPOAb identifies ongoing thyroid inflammation and destruction, marking active autoimmune processes that directly damage thyroid tissue. 1, 3
• TgAb may interfere with thyroglobulin measurement, potentially masking true thyroglobulin levels and complicating monitoring in thyroid cancer surveillance. 3
• Both antibodies can be present simultaneously, but when both are elevated, antibody concentrations are generally higher than when only one type is present. 5

When to Order Each Antibody

Primary Screening Scenarios (Order TPOAb First)

• Children with type 1 diabetes: Test for both anti-TPO and anti-thyroglobulin antibodies soon after diagnosis, as 17-30% will develop autoimmune thyroid disease. 4, 1, 2
• Suspected autoimmune thyroid disease: TPOAb is more predictive than TgAb for diagnosing autoimmune thyroid dysfunction. 2, 6
• Risk stratification for hypothyroidism: TPOAb-positive patients require TSH monitoring every 6-12 months due to their 4.3% annual progression risk. 1, 3

Specific Indications for TgAb

• Thyroid cancer monitoring: TgAb must be checked because its presence interferes with thyroglobulin measurement, potentially masking recurrent disease. 3
• When TPOAb is negative but clinical suspicion remains high: Some studies suggest TgAb may be positive more frequently than TPOAb in certain populations with Hashimoto's thyroiditis (up to 98.6% vs 81.4% in some assays). 7
• Comprehensive autoimmune evaluation: Order both antibodies together in children with type 1 diabetes or when establishing baseline autoimmune status. 4, 1

Diagnostic Performance Characteristics

Prevalence in Autoimmune Thyroid Disease

• Hashimoto's thyroiditis: TPOAb present in 99.3% of cases, TgAb in 74% of cases (though some studies show higher TgAb prevalence depending on assay used). 3, 7
• Graves' disease: TPOAb present in 74% of cases, with similar TgAb prevalence. 3, 6
• Both antibodies together: When both are positive, this indicates more severe autoimmune activity with higher antibody concentrations. 5

Critical Timing Considerations

Avoid testing thyroid function and antibodies during acute metabolic stress (hyperglycemia, ketosis, ketoacidosis, weight loss) as results may be misleading due to euthyroid sick syndrome. 4, 3 If tests are performed during metabolic instability, repeat them after achieving metabolic stability. 4, 3

Monitoring Strategy After Positive Results

• TPOAb-positive patients with normal TSH: Recheck TSH every 6-12 months, or more frequently if TSH is trending upward or symptoms develop. 1, 3
• Repeat antibody testing is not required after an initial negative result unless clinical signs or symptoms of thyroid or endocrine disease develop. 3
• Annual TSH measurement is recommended in individuals who test positive for TPO antibodies, even when baseline thyroid function is normal. 3

Associated Autoimmune Screening

When either antibody is positive, screen for other autoimmune conditions including:

• Type 1 diabetes: Check fasting glucose and HbA1c annually. 3
• Celiac disease: Measure IgA tissue transglutaminase antibodies with total serum IgA. 3
• Addison's disease: Consider screening with 21-hydroxylase antibodies (21OH-Ab) or adrenocortical antibodies. 3
• Pernicious anemia: Monitor B12 levels annually. 3

Common Pitfalls to Avoid

• Do not rely solely on TgAb for risk stratification – TPOAb is the superior predictor of progression to hypothyroidism. 1, 2
• Do not assume negative TPOAb rules out autoimmune thyroid disease – some patients may have isolated TgAb positivity, particularly in certain populations. 7
• Do not forget to check TgAb in thyroid cancer patients – its presence invalidates thyroglobulin as a tumor marker. 3
• Do not test during acute illness – wait for metabolic stability to avoid misleading results from euthyroid sick syndrome. 4, 3