Autoimmune Thyroid Disease - Thyroiditis

Key Points

Autoimmune thyroid disorders (AITDs) are among the most common autoimmune disorders. Antithyroid antibodies may be helpful in the subclassification of autoimmune thyroid disease.

Antibodies by biology, function, type, evidence of antibody damage, and clinical use

 

Thyroid peroxidase (TPO) antibodies

Thyroid Stimulating Hormone Receptor (TSHR) antibodies (TRAb)

Thyroglobulin (Tg) antibodies

Biology

TPO is a transmembrane protein essential for synthesis of thyroid hormones

TSHR, a TSH-specific receptor, controls thyroid function and cell growth

Tg is the precursor to thyroid hormones and is highly immunoreactive

Function

TPO is targeted by the thyroid microsomal antibody

  • TRAb targets TSHRs and competes with TSH for receptor binding
  • TRAb is not inhibited by the TSH feedback loop

Tg antibody is directed against thyroglobulin

Type

Polyclonal antibody (usually IgG1, IgG4)

  • 3 classes (IgG antibodies)
    • Stimulating antibodies
      • Also known as long-acting-thyroid stimulating antibodies (LATS) or thyroid-stimulating antibodies
    • Blocking antibodies
      • May be etiology of hypothyroidism
    • Neutral antibodies
  • Test characteristics
    • Measures both stimulating and blocking antibodies

Polyclonal antibody (most common is IgG1)

Evidence of antibody damage

  • No evidence for mediation of damage
    • TPO is a marker
  • Stimulating antibody
    • Mediates damage
  • Blocking antibody
    • Does not mediate damage
  • No evidence for mediation of damage
    • Tg is a marker

Clinical Use

Healthy populations

  • Detectable in a small percentage

Healthy populations

  • Not typically detected

Healthy populations

  • Detectable in a small percentage

Graves’ disease

  • Antibody present in ~80% of individuals
  • Presence of antibody is diagnostic for Graves, but not usually necessary for diagnosis

Graves’ disease

  • TRAb or thyroid-stimulating immunoglobulin (TSI) presence is diagnostic for Graves, but not usually necessary for diagnosis
    • Newer assays are equally accurate
  • Prognostic marker for relapse after treatment
  • Presence predicts risk of thyroid dysfunction in newborns born to mothers with current or treated Graves

Graves’ disease

  • Antibody present in 40-70% of individuals
  • Provides no additional information over TPO antibodies

Hashimoto thyroiditis

  • Antibody present in >90% of individuals
  • Most sensitive marker for disease
  • Not recommended for use in monitoring

Hashimoto thyroiditis

  • Antibody present in >90% of individuals
  • Presence of antibody is diagnostic, but provides no additional information over TPO antibodies

Postpartum thyroiditis

  • Antibody presence during pregnancy predicts risk of disease postpartum

Hashimoto thyroiditis

  • No indicated use in this disease

Thyroid cancer

  • Test use is most important for monitoring for thyroid cancer recurrence post ablation or total thyroidectomy
  • Tg antibodies may interfere with Tg measurements
    • Should be assessed with each Tg measurement

Subclinical hypothyroidism

  • May indicate increased risk of development of overt hypothyroidism

Postpartum thyroiditis

  • Antibody presence may predict postpartum thyroiditis

Diagnosis

Indications for Testing

  • Clinical evidence of hypo- or hyperthyroidism; family history of thyroid disease

Laboratory Testing

  • Thyroid stimulating hormone (TSH) followed by free T4 – establish presence of hypo- or hyperthyroidism
    • Hashimoto thyroiditis most likely if patient is hypothyroid
      • Elevated TSH and low free T4  
    • Graves' disease most likely if patient is hyperthyroid
      • Low TSH and elevated free T4
  • Antibody screening – if thyroid disease identified
  • Refer to Key Points section

Differential Diagnosis

Clinical Background

Thyroiditis is an inflammation of the thyroid gland and has multiple etiologies.

Epidemiology

  • Prevalence
    • 30-200/100,000 in adults
    • 1/10,000 in pediatric population
  • Age – peaks in 20s-40s
  • Sex – M<F

Classification of Autoimmune Thyroiditis

  • Graves' disease (form of hyperthyroidism)
  • Hashimoto thyroiditis (form of hypothyroidism)
    • Focal thyroiditis – may be a variant of Hashimoto thyroiditis
  • Acute
  • Subacute
    • Viral (organisms may include coxsackievirus, mumps virus, influenza virus, Epstein-Barr virus, adenoviruses)
      • de Quervain thyroiditis – tends to follow viral epidemics with seasonal and geographical distribution
    • Transient hyperthyroidism
      • Pregnancy-related (may also be linked to hyperemesis gravidarum)
      • Postpartum thyroiditis
    • Euthyroid sick syndrome (abnormal thyroid function associated with a nonthyroidal illness)
  • Silent (subclinical)
    • Excessive thyroid hormone therapy
    • Medication-induced

Risk Factors

  • Family history – genetic variations may predispose individuals to familial thyroid autoimmunity
  • Iodine deficiency – use of noniodized salt most common cause
  • Chronic illness or another other autoimmune disease (eg, diabetes mellitus type 1 [DM1], celiac disease)

Clinical Presentation

  • Hashimoto thyroiditis
    • Nontoxic goiter – result of gland enlargement; no overproduction of thyroid hormone
    • Slowly progressive disease
    • Hypothyroidism related to glandular destruction
  • Graves' disease
    • Diffuse toxic goiter – overproduction of thyroid hormone
    • 60-80% of thyrotoxicoses caused by Graves' disease
      • May present as thyroid storm – acute, life-threatening hypermetabolic state
    • Constitutional
      • Weight loss, heat and cold intolerance, fatigue
    • Cardiovascular
    • Ophthalmologic
      • Ophthalmopathy
      • Proptosis, usually bilateral
  • Autoimmune polyglandular syndrome type 2

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Assess thyroid function

Use in risk stratification of palpable thyroid nodule

Thyroid stimulating hormone (TSH) status should be known to properly interpret serum thyroglobulin levels

    
Thyroid Peroxidase (TPO) Antibody 0050075
Method: Quantitative Chemiluminescent Immunoassay

Distinguish thyroid autoimmune disorders from nonautoimmune disease or hypothyroidism

Determine risk in individuals with a familial history of autoimmune thyroid disease

Evaluate before beginning amiodarone, interferon alpha, interleukin-2, or lithium therapy

Not recommended for initial thyroid disorders testing

    
Thyroid Stimulating Hormone Receptor Antibody (TRAb) 2002734
Method: Quantitative Electrochemiluminescent Immunoassay

First-line testing for autoimmune thyroid disease

Distinguish Graves’ disease from factitious thyrotoxicosis, postpartum thyroiditis, or toxic nodular goiter

Prognostic marker for relapse of Graves’ disease or remission following drug therapy

Predict risk of thyroid dysfunction in newborns of mothers with Graves’ disease

Evaluate for the presence of euthyroid Graves’ophthalmopathy

    
Thyroglobulin Antibody 0050105
Method: Quantitative Chemiluminescent Immunoassay

Evaluate potentially unreliable thyroglobulin measurements in thyroid carcinomas

Diagnose autoimmune thyroid disease when antithyroid peroxidase (anti-TPO) autoantibody measurements are negative and a high clinical suspicion of autoimmune thyroid disease exists

Predict development of hypothyroidism in individuals with high-normal thyrotropin levels

    
Thyroid Antibodies 0050645
Method: Chemiluminescent Immunoassay

Aid in the differentiation between thyroid autoimmune disorders and nonautoimmune disease or hypothyroidism

May be useful in the setting of a negative anti-TPO autoantibody test with a high clinical suspicion of autoimmune thyroid disease

Not the preferred initial test for evaluation of autoimmune thyroid disorder; consider ordering Thyroid Peroxidase (TPO) Antibody

    
Thyroid Stimulating Immunoglobulin 0099430
Method: Quantitative Bioassay/Quantitative Chemiluminescent Immunoassay

Secondary testing for autoimmune thyroid disease in the following cases

  • Prognostic marker for relapse of autoimmune hyperthyroidism (Graves’ disease) or remission following drug therapy
  • Support Graves’ disease diagnosis in difficult (euthyroid) cases

Predict risk of thyrotoxicosis in newborns of mothers with Graves’ disease

    
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay

Preferred test for screening and monitoring thyroid function

Aid in the diagnosis of primary hyperthyroidism and differential diagnosis of hypothyroidism

Monitor individuals on thyroid hormone replacement therapy

Confirm suppression during thyroxine therapy for thyroid carcinoma

Do not order more than every 3-6 months
Thyroxine, Free (Free T4) 0070138
Method: Quantitative Electrochemiluminescent Immunoassay

Order following abnormal thyroid stimulating hormone (TSH) result to diagnose thyroid disease

Order in conjunction with TSH if pituitary (secondary) hypothyroidism is suspected

Assess thyroid status in pregnant women or those on estrogen supplementation, phenytoin, or salicylates

Monitor thyroid hormone replacement therapy during pregnancy and treatment of secondary hypothyroidism

Diagnostic Algorithm