Autoimmune Thyroid Disease

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
- Bacterial (most common organisms include Staphylococcus aureus, Streptococcus hemolyticus, Streptococcus pneumoniae)
- Thyroid tuberculosis (rare)
- Fungal (most commonly found in immunocompromised individuals)
- Radiation-induced (occurs ~2 weeks after high radiation exposure)
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 non-iodized salt most common cause
Chronic illness or another other autoimmune disease (eg, diabetes mellitus type 1 [DM1], celiac disease)

Clinical Presentation

Hashimoto thyroiditis
- Non-toxic 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
  - Tachycardia, high-output heart failure
- Ophthalmologic
  - Ophthalmopathy
  - Proptosis, usually bilateral
Autoimmune polyglandular syndrome type 2
- Presence of autoimmune thyroid disease with autoimmune adrenal insufficiency and/or DM1
- Associated conditions include celiac disease, primary hypogonadism, myasthenia gravis, vitiligo, alopecia, chronic atrophic gastritis (with or without pernicious anemia)

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
- Thyroid peroxidase (TPO) antibody – also known as thyroid microsomal antibody
  - Presence of antibody denotes autoimmune thyroid disease
    - Generally found in Hashimoto thyroiditis, Graves disease, postpartum thyroiditis and subacute thyroiditis
  - TPO antibodies found in euthyroid patients may indicate a risk for autoimmune thyroid disease
  - Presence of TPO antibodies may be associated with the following
    - Vitiligo
    - Pernicious anemia
    - DM1
    - Hypoparathyroidism
    - Celiac disease
    - Hypophysitis
    - Addison disease
- Thyroglobulin antibody (TgAb)
  - Less useful antibody compared to TPO in diagnosing autoimmune thyroid disease, but presence is diagnostic of Hashimoto thyroiditis
  - Presence may predict postpartum thyroiditis
  - Presence of TgAb antibodies may be associated with
    - Vitiligo
    - Pernicious anemia
    - DM1
    - Hypoparathyroidism
    - Celiac disease
    - Hypophysitis
    - Addison disease
- Thyroid stimulating hormone receptor antibody (TRAb)
  - Presence is diagnostic for Graves disease and responsible for hyperthyroidism
- Thyroid stimulating immunoglobulin (TSI)
  - Presence is indicative of Graves disease

Differential Diagnosis

Toxic nodular goiter
Thyroid cancer
Thyrotoxicosis factitia
Viral subacute thyroiditis
Pituitary tumor
Head and neck cancer

TPO antibodies
- Not recommended for use in monitoring Hashimoto thyroiditis
- No role in detection of malignancy
- Role in post-surgery monitoring for thyroid cancer
TRAb
- High level predictive of relapse after withdrawal of drug therapy
- Positive antibodies should be monitored each trimester in pregnant women
  - Positivity at end of pregnancy indicates fetal involvement likely
TSH and free T4
- Monitor change in medication dosing
- In pregnant women with positive TPO antibodies, use monthly TSH to monitor for development of hypothyroidism

Tests generally appear in the order most useful for common clinical situations

Test name: Thyroid Stimulating Hormone

ARUP #: 0070145

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Establish presence of hypo- or hyperthyroidism

Assess and monitor thyroid status

Functional sensitivity of assay is <0.02 mU/L

Follow-up:

If elevated or depressed, order free T4 or total T4

Test name: Thyroxine, Free (Free T4)

ARUP #: 0070138

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Establish presence of hypo- or hyperthyroidism

Assess and monitor thyroid status

Test name: Thyroglobulin Antibody

ARUP #: 0050105

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Aid in diagnosing Hashimoto thyroiditis

Substantiate thyroid disease in patients with nonthyroidal illness

May predict postpartum thyroiditis

Test name: Thyroid Stimulating Hormone Receptor Antibody (TRAb)

ARUP #: 2002734

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Discriminate between Graves disease and toxic nodular goiter

Diagnostic for Graves disease with hyperthyroidism

Determine appropriate course of therapy after diagnosis

Test name: Thyroid Peroxidase (TPO) Antibody

ARUP #: 0050075

Methodology: Quantitative Chemiluminescent Immunoassay

Use:

Aid in diagnosis of Hashimoto chronic thyroiditis

Presence of antibodies may suggest risk of autoimmune thyroid disease

Test name: Thyroid Antibodies

ARUP #: 0050645

Methodology: Chemiluminescent Immunoassay

Use:

Test for thyroid peroxidase (TPO) antibodies and TgAb

Diagnose Hashimoto thyroiditis, idiopathic hypothyroidism, and Graves disease

Predict progression of chronic thyroiditis

Test name: Thyroid Stimulating Immunoglobulin

ARUP #: 0099430

Methodology: Quantitative Bioassay/Quantitative Chemiluminescence

Use: Detect thyroid antibodies for diagnosing autoimmune disease (Graves disease)

Additional Tests Available

Test name: Thyroxine Binding Globulin

ARUP #: 0070410

Methodology: Quanititative Chemiluminescent Immunoassay

Comments:

Test name: Triiodothyronine, Total (Total T3)

ARUP #: 0070474

Methodology: Quantitative Electrochemiluminescent Immunoassay

Comments:

Test name: Triiodothyronine, Free (Free T3)

ARUP #: 0070133

Methodology: Quantitative Electrochemiluminescent Immunoassay

Comments:

Not preferred test for hypothyroidism

Confirm diagnosis of hyperthyroidism with a normal free T4 or total thyroxine (T4)

Test name: Triiodothyronine, Free by Equilibrium Dialysis/HPLC-Tandem Mass Spectrometry

ARUP #: 0093243

Methodology: Quantitative Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry

Comments:

Test name: Thyroxine

ARUP #: 0070140

Methodology: Quantitative Electrochemiluminescent Immunoassay

Comments:

Some research recommends using total T4 in place of free T4 during pregnancy (adjusting the reference interval upward by 1.5 times)

Test name: Thyroxine, Free by Equilibrium Dialysis/HPLC-Tandem Mass Spectrometry

ARUP #: 0093244

Methodology: Quantitative Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry

Comments:

Guidelines

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Published Guidelines. [Accessed: 28 Apr 2009]

General

ARUP Institute for Clinical and Experimental Pathology®

La'ulu SL, Slev PR, Roberts WL. Performance characteristics of 5 automated thyroglobulin autoantibody and thyroid peroxidase autoantibody assays. Clin Chim Acta. 2007; 376 (1-2) :88-95.PubMed

Comprehensive Review: October 2011
Last Update: October 2011