Can TPO Antibodies Be Tested After Starting Levothyroxine?
Yes, TPO antibodies can be ordered after starting levothyroxine, and the test remains clinically valid and useful for confirming Hashimoto's thyroiditis as the underlying cause of hypothyroidism. 1, 2
Why TPO Testing Remains Valid on Levothyroxine
- Levothyroxine does not eliminate TPO antibodies—it only reduces their levels gradually over time, with TPO antibodies becoming negative in only 16% of patients after a mean of 50 months of treatment 3
- The presence of TPO antibodies identifies an autoimmune etiology and predicts a higher risk of progression to overt hypothyroidism (4.3% per year versus 2.6% in antibody-negative individuals), making the diagnosis clinically important even after treatment has begun 1, 2
- Anti-TPO antibodies remain detectable in the vast majority of Hashimoto's patients despite levothyroxine therapy, with 92% of patients showing declining but still positive antibody levels over years of treatment 3
Clinical Utility of Testing TPO After Starting Levothyroxine
- Confirming autoimmune etiology helps guide long-term management, including screening for associated autoimmune conditions such as type 1 diabetes, celiac disease, Addison's disease, and pernicious anemia 1, 2
- Positive TPO antibodies justify more aggressive TSH targets in certain populations, particularly women planning pregnancy who require TSH <2.5 mIU/L before conception 1
- The diagnosis of Hashimoto's thyroiditis (confirmed by positive TPO antibodies) indicates the hypothyroidism is likely permanent, eliminating the need for future trials off medication 1
Expected Changes in TPO Antibodies on Levothyroxine
- TPO antibody levels decline in 92% of patients receiving levothyroxine, with a mean decrease of 45% after 1 year and 70% after 5 years 3
- After 15 months of levothyroxine treatment, studies show significant decreases in both anti-thyroglobulin and anti-thyroid peroxidase antibody levels 4
- In pediatric populations, levothyroxine therapy produces a significant decrease in anti-Tg antibody levels during follow-up 5
Important Caveats
- The absolute antibody level is less important than simply confirming their presence—even declining antibody titers on treatment still confirm the autoimmune diagnosis 3
- TPO antibodies cannot differentiate between Graves' disease and Hashimoto's thyroiditis, as they are present in 74% of Graves' patients and 99.3% of Hashimoto's patients, so clinical context (hypothyroidism versus hyperthyroidism) is essential 2
- Anti-thyroglobulin antibodies (TgAb) may interfere with thyroglobulin measurement, potentially complicating thyroid cancer monitoring if that becomes relevant in the future 2
When TPO Testing Is Most Useful After Starting Levothyroxine
- For patients started empirically on levothyroxine without prior antibody testing, checking TPO antibodies confirms whether the hypothyroidism is autoimmune versus other etiologies 1, 2
- For risk stratification in patients with TSH 4.5-10 mIU/L already on treatment, positive TPO antibodies support continuing therapy given the 4.3% annual progression risk 1
- To guide screening for associated autoimmune conditions that may develop over time in patients with confirmed autoimmune thyroid disease 2