TPO Antibodies vs TgAb: What Each One Tells You About Hashimoto's

TPO antibodies (thyroid peroxidase antibodies, also called anti-TPO or anti-microsomal antibodies) and TgAb (thyroglobulin antibodies, also called anti-thyroglobulin) are the two main antibodies tested in the workup of autoimmune thyroid disease, particularly Hashimoto's thyroiditis.

Both are immunoglobulin G (IgG) antibodies directed against proteins involved in thyroid hormone synthesis. They are markers of autoimmune attack on the thyroid gland and frequently appear together. However, they are not equivalent in clinical significance. TPO antibodies are elevated in 90 to 95% of Hashimoto's cases and 70 to 80% of Graves' disease cases. TgAb are elevated in 60 to 80% of Hashimoto's cases and in a smaller proportion of Graves' cases.

The proteins they target serve different roles: thyroid peroxidase is the enzyme directly responsible for synthesising thyroid hormone (it iodinates tyrosine residues and couples them into T3 and T4). Thyroglobulin is the large storage protein on which thyroid hormone is assembled and held before release. Antibodies against peroxidase directly interfere with hormone production. Antibodies against thyroglobulin are thought to reflect broader autoimmune activation without directly impairing the synthesis enzyme.

What they target: TPO antibodies attack thyroid peroxidase, the enzyme that makes thyroid hormone. TgAb attack thyroglobulin, the storage scaffold. Disrupting the enzyme (TPO) has more direct consequences for thyroid output.

Prevalence in Hashimoto's: TPO antibodies are present in 90 to 95% of confirmed Hashimoto's patients. TgAb are present in 60 to 80%. About 5 to 10% of Hashimoto's patients have TgAb but not TPO antibodies, which is why both are tested in the initial workup.

Clinical relevance in pregnancy: TPO antibodies carry most of the reproductive risk signal. The large RCTs (TABLET, T4LIFE), the 2025 meta-analysis, and the 2026 ATA guidelines all used TPO antibody positivity as the key inclusion criterion. The miscarriage rate data (approximately 26.7% vs 7.1% in TPO-positive vs TPO-negative women) refers specifically to TPO antibody status. TgAb positivity adds little additional pregnancy risk information beyond what TPO antibody status already provides.

Postpartum thyroiditis risk: TPO antibody positivity is the primary predictor. Women with high third-trimester TPO antibody titers face up to 80% risk of postpartum thyroiditis. TgAb titers in the third trimester are not used to stratify this risk in current guidelines.

Relevance to thyroid cancer monitoring: TgAb is clinically important in one context that TPO antibodies are not: monitoring thyroglobulin levels after thyroid cancer treatment. If TgAb are present, they interfere with the thyroglobulin assay used to detect cancer recurrence, making TgAb a critical co-test in that context. For Hashimoto's monitoring outside of cancer follow-up, TgAb adds little incremental value once TPO antibody status is known.

How they change with treatment: Both TPO antibodies and TgAb fall during pregnancy due to immune tolerance and are known to fall with selenium supplementation. Neither titer is used to guide levothyroxine dosing. Dose decisions are based on TSH and Free T4, not antibody levels.

Use TPO antibodies as the primary autoimmunity screen. If TPO antibodies are positive, you have confirmed thyroid autoimmunity. In Hashimoto's monitoring, pregnancy planning, and postpartum risk stratification, TPO antibody status is the clinically relevant result.

Add TgAb to the initial workup to catch the minority (5 to 10%) of Hashimoto's patients who are TPO-antibody-negative but TgAb-positive. Once the diagnosis is established, repeat TgAb testing during Hashimoto's monitoring adds little value.

Use TgAb in thyroid cancer follow-up. After total thyroidectomy for thyroid cancer, elevated TgAb invalidates the thyroglobulin tumour marker test and needs to be checked alongside every thyroglobulin measurement.

Do not recheck antibodies during pregnancy to guide treatment decisions. The 2026 ATA guidelines are explicit that antibody titers do not influence levothyroxine dosing during pregnancy. TSH and Free T4 are the monitoring markers.