Clinical Inquiries

How useful are autoantibodies in diagnosing thyroid disorders?

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They’re useful in diagnosing Graves’ disease and, to a lesser extent, autoimmune thyroid disease; they can also help predict hypothyroidism. thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves’ disease by a moderate to large degree (strength of recommendation [SOR]: B, cross-sectional study). A positive or negative thyroid peroxidase antibody (TPOAb) test increases or decreases the probability of autoimmune thyroid disease by only a small to moderate degree (SOR: B, 3 cross-sectional studies).

Thyroid-stimulating hormone (TSH) levels >2 mU/L, although still in the normal range, can be followed up with TPOAb testing to determine whether the patient has an increased probability of developing hypothyroidism (SOR: B, cohort study with a vague hypothyroidism reference standard).

Evidence summary

Although TSH followed by free T4 remain the initial screening tests for thyroid disorders, adding thyroid autoantibodies may refine the diagnosis. Three principal thyroid antibodies—TPOAb, thyroglobulin, and TRAb—can be positive in a variety of autoimmune thyroid disorders. TPOAb represents a specific antigen of antimicrosomal antibody (AMA). It has largely replaced AMA testing in most laboratories and clinical settings.

Antibodies point to Graves’, autoimmune disorders

A cross-sectional study of 267 Singaporean patients with previously diagnosed thyroid disorders measured TRAb, AMA, and thyroglobulin (TABLE). TRAb levels >10 U/L were found to have a positive likelihood ratio (LR+) of 13 and a negative likelihood ratio (LR–) of 0.2 for Graves’ disease.1

Two cross-sectional studies compared AMA to TPOAb in healthy patients and those with autoimmune thyroid and nonthyroid disorders. One study of 235 people in a university endocrinology department found that a TPOAb level >190 U/mL yielded an LR+ of 10.75 and an LR– of 0.15 for chronic autoimmune (Hashimoto’s) thyroiditis [CAHT]; the AMA-positive sera yielded an LR+ of 13.67 and an LR– of 0.19. Both TPOAb and AMA test characteristics were highly associated with CAHT (P<.001).

Autoimmune markers in thyroid disorders

% TRA b >3.4 U/L% TRA b >10 U/L% AMA positive% thyroglobulin positive
Thyroid disorders% of study patie ntsLR +LR –LR +LR –LR +LR –LR +LR –
Graves’ disease684.60.1130.
Subacute thyroiditis40.
Thyroid nodules60.23.402.
AMA, antimicrosomal antibodies; CAHT, chronic autoimmune (Hashimoto’s) thyroiditis; LR +, positive likelihood ratio; LR –, negative likelihood ratio; TRAb, thyrotropin receptor antibodies
Source: Khoo DHC, et al.1


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