Anti-TPO antibodies: what the test shows and why it matters for athletes

Antibodies to thyroid peroxidase (anti-TPO) are the main laboratory marker of autoimmune thyroid damage. For an athlete the thyroid gland is the “speed regulator” of metabolism: energy expenditure, heart rate, thermoregulation, and recovery all depend on it. The editorial team explains what exactly the anti-TPO test reveals, when it is worth taking, and how to understand the result correctly.

Thyroid peroxidase and antibodies to it

Thyroid peroxidase is an enzyme that works on the surface of thyroid cells. It oxidizes iodine and incorporates it into the protein thyroglobulin, and then “cross-links” the iodinated residues into the hormone molecules T4 and T3. Without this enzyme, the synthesis of thyroid hormones is impossible.

Antibodies to TPO are immunoglobulins of class G that the immune system produces against its own enzyme. Their appearance indicates that the body perceives thyroid tissue as foreign. The antibodies themselves are probably not the main destructive factor, but they reflect the activity of the autoimmune process.

In parallel, lymphocytes accumulate in the gland and gradually destroy the thyrocytes. Over time the amount of functional tissue decreases, and the gland stops producing enough hormones. This process is called chronic autoimmune thyroiditis, or Hashimoto's thyroiditis.

Antibodies to TPO are detected not only in Hashimoto's but also in most patients with Graves' disease, and in some people with other autoimmune conditions, for example type 1 diabetes or celiac disease.

What the test shows

A positive anti-TPO test means the presence of an autoimmune process in the thyroid gland, but not necessarily an impairment of its function. The large American NHANES III study showed that antibodies to TPO are detected in roughly one in ten adults, more often in women and with age.

The practical value of the antibodies is prognostic. The Whickham survey demonstrated that in people with antibodies the risk of developing hypothyroidism is markedly higher, especially if TSH is already at the upper limit or elevated. In such a combination the risk is a few percent per year.

The antibody level does not correlate directly with the severity of the disease. A person with a very high titer may have normal gland function, while another with moderate antibodies has already developed hypothyroidism. That is why TSH and free T4 are assessed first of all, and the antibodies help explain the cause.

For diagnosing Graves' disease, antibodies to the TSH receptor are more important than those to TPO. Anti-TPO in this case only confirm the autoimmune nature of the process.

Who should take the test and when

The anti-TPO test is not part of annual routine examinations. It is ordered for specific indications, primarily with elevated TSH, to find out the cause of hypothyroidism, and with enlargement of the thyroid gland or nodules.

• elevated or borderline high TSH;
• goiter or heterogeneous gland structure on ultrasound;
• planning pregnancy in women with a burdened history;
• other autoimmune diseases in the personal or family history;
• unexplained fatigue, cold intolerance, weight gain not accounted for by training.

Unlike TSH, antibodies usually do not need to be repeated often. If a positive result has already been obtained, further monitoring concerns gland function, not the antibody titer. Repeat measurements rarely change management.

For women planning a pregnancy, the presence of antibodies has separate significance. The 2017 guidelines of the American Thyroid Association regard positive anti-TPO as a risk factor for complications and grounds for more careful monitoring of TSH during pregnancy.

It is important for athletes to remember that the symptoms of hypothyroidism — fatigue, decreased performance, slow recovery — are easily confused with overtraining. The test helps distinguish these states.

Why this matters specifically for athletes

Thyroid hormones determine the basal metabolic rate, cardiac contractility, the use of fats and carbohydrates, and thermoregulation. Even moderate hypothyroidism can reduce endurance, increase recovery time, and contribute to gaining fat mass.

A situation specific to sport is energy deficiency. With prolonged undereating the body lowers active T3 to conserve energy, and the picture resembles hypothyroidism. However, antibodies to TPO are not the cause in this case, and treatment consists of restoring nutrition, not hormones.

Separately, the editorial team cautions against the self-administration of thyroid hormones for “cutting”. An excess of T3 or T4 suppresses the gland's own function, causes tachycardia and rhythm disturbances, and loss of muscle mass and bone tissue. This is not a way to compensate for detected antibodies.

For athletes with confirmed hypothyroidism, replacement therapy with levothyroxine, selected by an endocrinologist, allows normal training and competition. Levothyroxine is not on the WADA Prohibited List.

How to prepare and which factors distort the result

Blood for anti-TPO is taken in the morning, preferably on an empty stomach. Particular attention should be paid to biotin (vitamin B7), which is often part of “hair and nail” complexes and sports multivitamins in high doses.

Biotin can distort the results of immunochemical assays that use the streptavidin-biotin system. Depending on the test format, both falsely elevated and falsely reduced results of TSH, hormones, and antibodies are possible. The FDA has issued a specific warning about this risk.

Laboratories usually advise stopping high-dose biotin at least a few days before the test, but the exact interval should be checked with the laboratory. The doctor should be informed about taking any supplements.

Other factors — an acute illness, recent administration of iodine-containing contrast, and pregnancy — can affect thyroid function and the interpretation of the whole panel. Results obtained during such periods are better rechecked.

Editorial conclusions

Antibodies to TPO are a marker of an autoimmune process in the thyroid gland, not a standalone diagnosis. A positive result indicates an increased risk of hypothyroidism and requires periodic monitoring of TSH, but not treatment automatically.

For athletes the test is useful for distinguishing autoimmune damage from adaptation to energy deficiency and overtraining. Proper preparation, in particular avoiding biotin before the test, makes the result more reliable.

The editorial team also suggests reviewing our materials on the causes of elevated antibodies to TPO, on TSH and free T4 in athletes, and on RED-S syndrome and thyroid hormones.

References

1. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22(12):1200–1235.
2. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–1751.
3. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489–499.
4. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43(1):55–68.
5. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13(4–5):391–397.
6. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27(3):315–389.