Autoimmune Thyroiditis

Thyroiditis refers to inflammation of the thyroid gland. There are many etiologies of thyroiditis, including silent or subclinical thyroiditis, transient hyperthyroidism, acute and subacute infectious thyroiditis, and chronic autoimmune thyroiditis (Graves disease and Hashimoto thyroiditis). Thyroid function tests are used to confirm thyroid disease; depending on results, antithyroid antibody tests may be useful to confirm an autoimmune cause of thyroiditis. Antithyroid antibody tests include tests for thyroid peroxidase (TPO) autoantibodies (TPOAb), thyroid stimulating hormone (TSH) receptor autoantibodies (TRAb), and thyroglobulin (Tg) autoantibodies (TgAb).  

Quick Answers for Clinicians

When should Hashimoto thyroiditis be suspected?

Hashimoto thyroiditis is a slowly progressing disease. Symptoms suggestive of Hashimoto thyroiditis include several nonspecific symptoms of hypothyroidism, such as fatigue, constipation, dry skin, bradycardia, and depression. The thyroid gland may be enlarged and firm. Hashimoto thyroiditis should be suspected in patients with elevated thyroid stimulating hormone (TSH) and low thyroxine (T4) concentrations.

When should Graves disease be suspected?

Symptoms suggestive of Graves disease include nonspecific symptoms of hyperthyroidism, including weight loss, heat intolerance, and tachycardia. Signs may include exophthalmos and a diffuse and enlarged thyroid. Thyroid storm, an acute and life-threatening metabolic state, may occur. Graves disease should be suspected in patients with low thyroid stimulating hormone (TSH) and elevated thyroxine (T4) concentrations.

What is autoimmune polyglandular syndrome type 2, and how does it manifest?

Autoimmune polyglandular syndrome type 2 refers to the presence of autoimmune thyroid disease with autoimmune adrenal insufficiency and/or type 1 diabetes mellitus. Associated conditions include celiac disease, primary hypogonadism, myasthenia gravis, vitiligo, alopecia, and chronic atrophic gastritis (with or without pernicious anemia).

What are thyroid autoantibodies, and how are they used in the evaluation of autoimmune thyroiditis?

Thyroid autoantibodies are antibodies produced by the body against the thyroid gland. The thyroid autoantibodies most frequently tested in clinical practice are thyroid peroxidase autoantibodies (TPOAb), thyroglobulin autoantibodies (TgAb), and thyroid stimulating hormone (TSH) receptor antibodies (TRAb). There are three classes of TRAb, named for their effect on the TSH receptor: stimulating, blocking, and neutral. Hashimoto thyroiditis, an autoimmune disorder that often results in hypothyroidism, is often associated with TPOAb. Graves disease, an autoimmune disorder that typically results in hyperthyroidism, is usually associated with stimulating TRAb (also referred to as thyroid stimulating immunoglobulin [TSI]). Other thyroid autoantibodies may also cause forms of autoimmune thyroiditis. For example, blocking TRAb may lead to hypothyroidism. Testing for thyroid autoantibodies is therefore useful in identifying the etiology of thyroid disease. However, thyroid autoantibody testing is not necessary or recommended for monitoring treatment response or disease progression. Thyroid autoantibody testing may also be useful in predicting the risk of thyroid disease; for example, women who are known to have high concentrations of TPOAb are at increased risk for developing hypothyroidism during pregnancy. Thyroid autoantibodies may interfere with thyroid hormone immunoassays; for more information, see the ARUP Consult Analytical Considerations in the Evaluation of Thyroid Function topic.

Which testing algorithms are related to this topic?

Indications for Testing

Laboratory testing is used to differentiate autoimmune-mediated thyroid disease (eg, Graves disease or Hashimoto thyroiditis) from other etiologies of hyper- or hypothyroidism, as well as to predict the risk of fetal thyroid dysfunction in mothers with a history of Graves disease and to investigate a potential autoimmune etiology of recurrent miscarriage.

Laboratory Testing

Initial Evaluation

Autoantibody testing may be performed after hypothyroidism or hyperthyroidism has been confirmed by TSH and free thyroxine (T4) testing. Hashimoto thyroiditis is the most likely form of autoimmune thyroiditis if the patient has hypothyroidism (elevated TSH and low free T4 concentrations), whereas Graves disease is most likely if the patient has hyperthyroidism (low TSH and elevated free T4 concentrations). For more information on the initial evaluation of suspected autoimmune thyroid disease, see the ARUP Consult Initial Evaluation of Thyroid Function topic.

Autoantibody Tests

Testing for antithyroid antibodies (TPOAb, TRAb, and TgAb) may be helpful for the diagnosis, monitoring, and prognosis of autoimmune thyroid disease when the clinical picture is unclear. This table presents the biological activity and use of tests for these antibodies in autoimmune thyroid disease.

Antithyroid Antibodies by Biology, Mechanism, Type, Evidence of Tissue Damage, and Clinical Use
  TPOAb TRAb TgAb
Biology TPO is a transmembrane protein essential for synthesis of thyroid hormones TSH-specific receptor controls thyroid function and cell growth Tg is the precursor to thyroid hormones and is highly immunoreactive
Mechanism Targeted by thyroid microsomal antibody

TRAb targets TSH receptors and competes with TSH for receptor binding

TRAb activity is not affected by TSH concentrations

TgAb is directed against Tg
Type Polyclonal antibody (usually IgG1, IgG4)

3 classes (IgG antibodies)a

  • Stimulating antibodies (also known as LATS or TSIs); may lead to Graves disease
  • Blocking antibodies; may result in hypothyroidism
  • Neutral antibodies
Polyclonal antibody (IgG1 most common)
Evidence of tissue damage None

TSI may cause tissue damage

Blocking antibody does not cause tissue damage

None
Clinical use Healthy Populations
Detectable in a very small percentage Not typically detected Detectable in a small percentage
Graves Disease

Present in ~80% of individuals with GD

Presence is diagnostic for GD, but TPOAb testing is not usually performed because TRAb is diagnostic and most sensitive

Presence may aid in differentiation of GD from factitious thyrotoxicosis, postpartum thyroiditis, or toxic nodular goiter

TPOAb testing may be considered to identify autoimmune thyroiditis in patients with thyroid nodules

TRAb or TSI presence is pathognomonic for GD but not usually necessary for diagnosis unless clinical picture is unclear (eg, in euthyroid cases); newer assays (eg, third generation) are more accurate

Prognostic marker for relapse after GD treatment

Test results aid in the differentiation of GD from factitious thyrotoxicosis, postpartum thyroiditis, or toxic nodular goiter

TRAb testing can be used to evaluate for the presence of euthyroid GD ophthalmopathy

Present in 40-70% of individuals with GD

TgAb testing provides no additional information over TRAb or TPOAb results; not recommended for the initial evaluation of autoimmune thyroid disease

TgAb testing may be useful when TPOAb measurements are negative and a high clinical suspicion exists for autoimmune thyroid disease

Hashimoto Thyroiditis

Present in >90% of individuals with HT

Presence is pathognomonic for HT

TPOAb testing is not recommended for HT monitoring

Not present in those with HT

Present in 60-80% of individuals with HT

Presence of TgAb is diagnostic for HT, but provides no additional information over TPOAb results (TgAb tests are less sensitive and specific than TPOAb)

TgAb testing may be useful when TPOAb measurements are negative and a high clinical suspicion exists for autoimmune thyroid disease

Pregnancy

Present in up to 18% of pregnant women

Presence during pregnancy predicts risk for postpartum thyroiditis

TPOAb testing may be used to evaluate individuals with recurrent miscarriage, with or without infertility issues

Follow-up with TPOAb testing is appropriate in pregnant women with TSH >2.5 mU/L

Presence predicts increased risk of thyroid dysfunction in newborns born to mothers with current GD

Presence may predict development of fetal or neonatal GD in patients with hypothyroidism who have been treated for GD (radioactive iodine ablation or thyroidectomy before pregnancy)

Present in up to 18% of pregnant women

Presence may predict postpartum thyroiditis

Subclinical Hypothyroidism
Presence may predict progression to overt hypothyroidism Not present Presence may predict progression to overt hypothyroidism
Thyroid Cancer
Not present Not present

TgAb testing is primarily used to monitor for thyroid cancer recurrence (after ablation or total thyroidectomy) and to investigate potentially unreliable Tg measurements in thyroid carcinoma

TgAb may interfere with Tg measurements and should be assessed with each Tg measurement

aClassified based on effect on TSH receptor. TRAb tests measure stimulating (TSI), blocking, and neutral autoantibodies. Standalone tests are available for TSI. TRAb and TSI in combination can be useful in unusual cases of hypothyroidism, such as hashitoxicosis.

GD, Graves disease; HT, Hashimoto thyroiditis; IgG, immunoglobulin G; LATS, long-acting thyroid stimulating autoantibodies; TSI, thyroid stimulating immunoglobulin

Sources: Ross, 2016 ; Garber, 2012 ; Alexander, 2017 

ARUP Laboratory Tests

Primary test for Hashimoto thyroiditis; secondary test for Graves disease

Acceptable secondary test for autoimmune thyroid disease; may be particularly useful in Graves disease

Acceptable secondary test for autoimmune thyroid disease; tests for stimulating class of TRAb

Not recommended for the initial evaluation of autoimmune thyroid disease

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