What autoantibody labs should be ordered to evaluate for autoimmune thyroiditis, specifically for conditions like Hashimoto's thyroiditis?

Autoantibody Testing for Autoimmune Thyroiditis

Order both anti-thyroid peroxidase (TPO) antibodies and anti-thyroglobulin (TgAb) antibodies to evaluate for autoimmune thyroiditis, as testing TPO alone misses 6-25% of Hashimoto's thyroiditis cases that have isolated TgAb positivity. 1, 2, 3

Primary Antibody Panel

Anti-Thyroid Peroxidase (TPO) Antibodies:

• TPO antibodies are the most sensitive marker for autoimmune thyroid disease, present in approximately 75-92% of Hashimoto's thyroiditis patients 1, 2, 4
• TPO antibodies are also positive in 70-82% of Graves' disease patients 2, 4
• TPO antibodies correlate with the degree of lymphocytic infiltration in the thyroid gland 4
• TPO antibodies are more predictive of thyroid dysfunction than TgAb in multivariate analysis 1

Anti-Thyroglobulin (TgAb) Antibodies:

• TgAb should be measured simultaneously with TPO antibodies, as 6% of Hashimoto's thyroiditis patients have isolated TgAb positivity without TPO antibodies 2
• Recent studies using sensitive immunoassays show TgAb prevalence (96-99%) actually exceeds TPO antibody prevalence (75-82%) in Hashimoto's thyroiditis 3, 5
• TgAb alone is positive in a significant subset of patients with painless thyroiditis (73.5% vs 33% for TPO) 3
• The diagnostic specificity of TgAb is comparable to TPO antibodies (92.4% vs 92.7%) 2

Thyroid Function Tests to Order Concurrently

Measure these simultaneously with antibody testing:

• Thyroid-stimulating hormone (TSH) at diagnosis when clinically stable or after glycemic control is established in diabetic patients 1
• Free thyroxine (FT4) should be measured if TSH is abnormal, as TSH alone can be misleading in central hypothyroidism or during acute metabolic stress 1, 6
• Avoid testing during acute metabolic decompensation (hyperglycemia, ketosis, weight loss) as results may show euthyroid sick syndrome 6

Critical Timing Considerations

When to test:

• Test soon after diagnosis of type 1 diabetes, as 25% of children with type 1 diabetes have thyroid autoantibodies at diagnosis 1, 6
• Recheck TSH every 1-2 years if initial testing is normal, or sooner if symptoms develop 1
• More frequent monitoring (every 6 months) is warranted if TSH is trending upward or if thyroid antibodies are positive 6

Common Pitfalls to Avoid

Do not rely on TPO antibodies alone:

• Using only TPO testing misses 6% of Hashimoto's thyroiditis cases with isolated TgAb positivity 2
• Some studies show TgAb has higher diagnostic sensitivity than TPO in certain populations 3, 5

Interpret results in clinical context:

• Thyroid antibodies occur in 5% of healthy individuals at standard dilutions, so positive results require clinical correlation 7
• TgAb can interfere with thyroglobulin measurement in thyroid cancer monitoring 6
• Different laboratory platforms produce varying results, making direct comparison across laboratories problematic 6

Timing matters:

• Testing during acute illness, ketoacidosis, or metabolic instability produces misleading results due to euthyroid sick syndrome 6
• If initial tests are performed during metabolic instability, repeat after achieving stability 6

Screening for Associated Autoimmune Conditions

Consider additional testing based on clinical presentation:

• Screen for celiac disease with IgA tissue transglutaminase antibodies (with total serum IgA) 1, 6
• Screen for type 1 diabetes with fasting glucose and HbA1c annually 6
• Consider 21-hydroxylase antibodies for Addison's disease if symptoms of adrenal insufficiency are present 1, 6
• Monitor B12 levels annually for pernicious anemia 6

The combination of TPO and TgAb testing provides optimal diagnostic sensitivity (approaching 99%) while maintaining high specificity (>92%) for autoimmune thyroiditis. 2, 3