Thyroiditis, Autoimmune - Autoimmune Thyroiditis

Primary Author: Straseski, Joely A., PhD, MS, MT(ASCP), DABCC.

  • Key Points
  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Content

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 – measures both stimulating and blocking antibodies

Polyclonal antibody (IgG1 most common)

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 very small percentage Not typically detected Detectable in a smaller percentage
Graves disease (GD)

Present in ~80% of individuals

Presence of antibody is diagnostic for GD, but not usually performed since TRAb is diagnostic and most sensitive

TRAb or thyroid-stimulating immunoglobulin (TSI) presence is pathognomonic for GD, but not usually necessary for diagnosis unless clinical picture unclear

  • Newer assays (eg, third generation) are even more accurate

Prognostic marker for relapse after treatment

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

Present in 40-70% of individuals

Provides no additional information over TRAb or TPO antibodies

Hashimoto thyroiditis (HT)

Present in >90% of individuals

Presence of antibody is pathognomonic for HT

Not recommended for use in monitoring

No indicated use in this disease

Present in 60-80% of individuals

Presence of antibody is diagnostic, but provides no additional information over TPO antibodies (less sensitive and specific than TPO)

Postpartum thyroiditis

Presence during pregnancy predicts risk of disease postpartum

No indicated use in this disease

Presence may predict postpartum thyroiditis

Subclinical hypothyroidism

May indicate increased risk of development of overt hypothyroidism

No indicated use in this disease No indicated use in this disease
Thyroid cancer
No indicated use in this disease No indicated use in this disease

Most important in monitoring for thyroid cancer recurrence (post ablation or total thyroidectomy)

Tg antibodies may develop and interfere with Tg measurements

Should be assessed with each Tg measurement

Indications for Testing

  • Differentiate autoimmune-mediated thyroid disease (eg, Graves disease [GD], Hashimoto thyroiditis [HT]) from other etiologies for hyper- or hypothyroidism
  • Predict risk of fetal thyroid dysfunction in mothers with history of GD
  • Establish an autoimmune cause for recurrent miscarriage

Laboratory Testing

  • Thyroid stimulating hormone (TSH) followed by free T4 – establish presence of hypo- or hyperthyroidism
    • HT – most likely if patient is hypothyroid
      • Elevated TSH and low free T4
    • GD – most likely if patient is hyperthyroid
      • Low TSH and elevated free T4
  • Antibody screening – as a follow-up when thyroid disease identified
    • Refer to Key Points section

Differential Diagnosis

Thyroid Disorders Testing Algorithm

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

Epidemiology

  • Prevalence
    • Graves disease (GD) – 20-30/100,000 (Burch, 2015)
    • Hashimoto thyroiditis (HT) – 1/1,000
  • Age
    • GD – 40s-50s (peak)
    • HT – 40s (peak)
  • Sex
    • GD – M<F, 1:5
    • HT – M<F, 1:8

Classification of Autoimmune Thyroiditis

  • Acute
  • Subacute
  • Transient hyperthyroidism
    • Pregnancy-related – may also be linked to hyperemesis gravidarum)
    • Postpartum thyroiditis – may become persistent
    • Euthyroid sick syndrome – abnormal thyroid function associated with a nonthyroidal illness)
  • Silent (subclinical)
    • Excessive thyroid hormone therapy
    • Medication-induced
  • Chronic – usually autoimmune
    • GD – causes hyperthyroidism
    • HT – causes hypothyroidism
      • Fibrous variant
      • Ig4-related variant
      • Juvenile variant
      • Hashitoxicosis variant

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)
  • Tobacco use for HT

Clinical Presentation

  • HT
    • Slowly progressive disease
    • Constitutional – fatigue
    • Gastrointestinal – constipation
    • Skin – yellow, dry, and cold
    • Endocrine – enlarged, firm thyroid gland
    • Cardiovascular – bradycardia
    • CNS – memory loss, depression
  • GD
    • Symptoms of thyrotoxicosis
      • Endocrine
        • Diffuse enlargement of gland (goiter)
        • May present as thyroid storm – acute, life-threatening hypermetabolic state
      • Constitutional
        • Weight loss, heat and cold intolerance, fatigue
      • Cardiovascular
      • Ophthalmologic
        • Ophthalmopathy – exophthalmos
        • Proptosis, usually bilateral
      • Skin
        • Dermopathy – nonpitting edema (rare)
  • 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

Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

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

Limitations

Blocking antibodies specific to TSHR may decrease TSI antibody levels; net response is most likely physiologic

TSH serum levels ≥6 mU/L may cause a false-positive result

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

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

Thyroglobulin Antibody 0050105
Method: Quantitative Chemiluminescent Immunoassay

Thyroid Antibodies 0050645
Method: Chemiluminescent Immunoassay

Additional Tests Available

Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay

Comments

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

Comments

Not the preferred initial thyroid disorder screening test

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

Guidelines

Bahn R, Burch H, Cooper D, Garber J, Greenlee C, Klein I, Laurberg P, McDougall R, Montori V, Rivkees S, Ross D, Sosa J, Stan M, American Thyroid Association, American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011; 17(3): 456-520. PubMed

Baloch Z, Carayon P, Conte-Devolx B, Demers L, Feldt-Rasmussen U, Henry J, LiVosli V, Niccoli-Sire P, John R, Ruf J, Smyth P, Spencer C, Stockigt J, Guidelines Committee, National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003; 13(1): 3-126. PubMed

Garber J, Cobin R, Gharib H, Hennessey J, Klein I, Mechanick J, Pessah-Pollack R, Singer P, Woeber K, American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012; 18(6): 988-1028. PubMed

General References

Burch HB, Cooper DS. Management of Graves Disease: A Review. JAMA. 2015 Dec15;314(23):2544-54. PubMed

Caturegli P, De Remigis A, Rose N. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014; 13(4-5): 391-7. PubMed

Caturegli P, Kimura H, Rocchi R, Rose N. Autoimmune thyroid diseases. Curr Opin Rheumatol. 2007; 19(1): 44-8. PubMed

Eckstein A, Esser J, Mann K, Schott M. Clinical value of TSH receptor antibodies measurement in patients with Graves' orbitopathy. Pediatr Endocrinol Rev. 2010; 7 Suppl 2: 198-203. PubMed

Galofre J, Davies T. Autoimmune thyroid disease in pregnancy: a review. J Womens Health (Larchmt). 2009; 18(11): 1847-56. PubMed

Menconi F, Marcocci C, Marinò M. Diagnosis and classification of Graves' disease. Autoimmun Rev. 2014; 13(4-5): 398-402. PubMed

Sweeney L, Stewart C, Gaitonde D. Thyroiditis: an integrated approach. Am Fam Physician. 2014; 90(6): 389-96. PubMed

Zöphel K, Roggenbuck D, Wunderlich G, Schott M. Continuously increasing sensitivity over three generations of TSH receptor autoantibody assays. Horm Metab Res. 2010; 42(12): 900-2. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Medical Reviewers

Last Update: January 2016