Antithyroid Antibody
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Antithyroid antibody studies are used to evaluate for autoimmune thyroid problems.
The reference ranges for antithyroid antibodies are as follows: [1]
Thyroid peroxidase antibody (TPOAb): Less than 35 IU/mL
Thyroglobulin antibody (TgAb): Less than 20 IU/mL
Thyroid-stimulating immunoglobulin antibody (TSI): Less than 140% of basal activity
Thyroid-stimulating hormone (TSH) receptor binding inhibitor immunoglobulin (TBII)/TRAb: 1.75 IU/L or less
Antibodies directed against 3 major thyroid antigens are as follows:
Thyroglobulin: Antithyroglobulin antibody (TgAb)
Thyroid peroxidase (microsomal antigen): Antithyroid peroxidase antibody (TPOAb)
TSH receptor: Anti-TSH receptor antibody (TRAb)
The presence of serum thyroid antibodies usually indicates an autoimmune thyroid disorder, but elevated levels may also be detected in other conditions.
Conditions associated with elevated serum TPOAb levels include the following:
Hashimoto disease (90%-100%) [2, 3]
Graves disease (50%-80%) [4]
Other autoimmune diseases (eg, type 1 diabetes mellitus) (40%)
Pregnancy (14%)
Sporadic multinodular goiter, isolated thyroid nodule, and thyroid cancer
Relatives of patients with an autoimmune thyroid disorder (40%-50%) may have elevated serum TPOAb levels.
Conditions associated with elevated serum TgAb levels include the following:
Hashimoto disease (80%-90%)
Graves disease (50%-70%) [4]
Other autoimmune diseases (eg, type 1 diabetes mellitus) (40%)
Pregnancy (14%)
Sporadic multinodular goiter, isolated thyroid nodule, and thyroid cancer
Relatives of patients with an autoimmune thyroid disorder (40%-50%) may have elevated serum TgAb levels.
Assays for TgAb and TPOAb are highly sensitive but less specific; therefore, the absolute concentration is very important in the interpretation of the test. Monitoring antibody titers is important to evaluate the disease progression/regression over time, as well as among different patients, but the same assay should be used for this purpose.
TRAb are classified as stimulating, blocking, and neutral antibodies in relation to thyroid function and can be measured with 2 techniques. The TSI bioassay is used to measure the net stimulatory activity of all TRAb, and the TBII assay is used to measure all 3 types of TRAb. In some laboratories, TRAb refers exclusively to the TBII assay.
Conditions associated with elevated serum TSI levels include the following:
Graves disease (80%-90% of untreated patients)
Toxic multinodular goiter (15%)
Conditions associated with elevated serum TBII levels include the following:
Graves disease (>90% of untreated patients)
Hashimoto disease (15%)
Specimen type: Blood serum; hemolyzed specimen not acceptable
Collection tube: Red-top tube or gel-barrier tube
Specimen preparation: Separate serum from cells and transfer to transport tube
Storage/transport temperature: Refrigerated
Stability: 7 days refrigerated, 1 month frozen
Patient instruction: No need for fasting
Specimen type: Blood serum; hemolyzed specimen not acceptable
Collection tube: Red-top tube or gel-barrier tube
Specimen preparation: Separate serum from cells and transfer to transport tube
Storage/transport temperature: Refrigerated
Stability: 7 days refrigerated, 1 month frozen
Patient instruction: No need for fasting
Specimen type: Blood serum
Collection tube: Red-top tube or gel-barrier tube
Specimen preparation: Separate serum from cells and transfer to transport tube
Storage/transport temperature: Refrigerated or frozen
Stability: 7 days refrigerated, 3 months frozen
Patient instruction: No need for fasting
Specimen type: Blood serum; hemolyzed specimen not acceptable
Collection tube: Red-top tube or gel-barrier tube
Specimen preparation: Separate serum from cells and transfer to transport tube
Storage/transport temperature: Frozen
Stability: 3 days refrigerated, 1 month frozen:
Patient instruction: No need for fasting
Autoimmune thyroid disease, including Hashimoto disease and Graves disease, is characterized by lymphocytic infiltration. Animal studies have shown that B lymphocytes in the thyroid gland are the major source of antithyroid antibodies. As described above, 3 major thyroid antibodies exist: TPOAb, TgAb, and TRAb.
TPOAb and TgAb are polyclonal antibodies of the immunoglobulin G (IgG) class. They have a complement fixing and cytotoxic capacity, but their role in Hashimoto disease still is not clear and seems to be a response to thyroid injury.
TRAb are divided into 3 types: stimulating, blocking, and neutral antibody in relation to the thyroid function. The stimulating TRAb are oligoclonal antibodies of the immunoglobulin G1 (IgG1) subclass. TRAb bind to TSH receptors and activate the signaling pathway. They can induce thyroid growth, as well as thyroid hormone production and secretion; this finding suggests that TRAb are the primary cause of Graves disease.
It is now believed that Graves disease and Hashimoto disease are closely related. In Graves disease, the goiter can result from TSH receptor stimulation, whereas, in Hashimoto disease, it results from lymphocytic infiltration, causing follicular cell destruction.
Indications for TSI and TRAb/TBII measurements include the following:
For diagnostic purposes in euthyroid patients with exophthalmos or other extrathyroidal manifestation or when thyroid uptake and scan is contraindicated or nondiagnostic
In pregnant women with Graves disease to determine the likelihood of neonatal thyrotoxicosis (risk increases with antibody concentration)
To assess the degree of disease activity
To assess the risk of Graves disease relapse after treatment with antithyroid agents (risk increases with antibody concentration)
To differentiate between gestational thyrotoxicosis and Graves disease in the first trimester of pregnancy
TSI and TRAb/TBII measurements are not routinely indicated for the diagnosis of Graves disease.
Indications for TPOAb measurement include the following:
To help confirm the diagnosis of Hashimoto disease (in some cases)
To help with the treatment decision in the patient with subclinical hypothyroidism (in some cases)
Indications for TgAb measurement include the following:
In conjunction with other thyroid antibody tests for diagnosis of autoimmune thyroid disease
To monitor the disease status of thyroid canceraftertreatment
Persistence of TgAb in patients with thyroid cancer for more than 1 year after therapy indicates the presence of residual thyroid tissue and perhaps an increased risk of recurrence.
High TPOAb levels in pregnant euthyroid women increases the risk of spontaneous miscarriage and preterm birth. Treatment with levothyroxine in these women seems to decrease the miscarriage rate, but it is not yet recommended to treat pregnant euthyroid women with positive antibody test results. [5, 6]
An elevated serum level of TPOAb and/or TgAb is essential for the diagnosis of the controversial disorder of Hashimoto encephalopathy.
TBII assays are less expensive and more precise in detecting TRAb than the TSI bioassay.
Appendix: Normal Hormone Reference Ranges. Greenspan’s Basic & Clinical Endocrinology. 9th ed. the McGraw-Hill Companies; 2011.
Bozic Antic I, Macut D, Popovic B, Isailovic T, Petakov M, Ognjanovic S, et al. Recurrent spontaneous abortions, Hashimoto thyroiditis and alopecia totalis: response to anticoagulation and intravenous immunoglobulin therapy. Gynecol Endocrinol. 2014 Feb. 30(2):100-2. [Medline].
Yu HJ, Lee J, Seo DW, Lee M. Clinical Manifestations and Treatment Response of Steroid in Pediatric Hashimoto Encephalopathy. J Child Neurol. 2013 Sep 20. 29(7):938-942. [Medline].
Jevalikar G, Solis J, Zacharin M. Long-term outcomes of pediatric Graves’ disease. J Pediatr Endocrinol Metab. 2014 Jun 19. [Medline].
Chen L, Hu R. Thyroid autoimmunity and miscarriage: a meta-analysis. Clin Endocrinol (Oxf). 2011 Apr. 74(4):513-9. [Medline].
Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011. 342:d2616. [Medline].
Chung JK, Park YJ, Kim TY, So Y, Kim SK, Park DJ. Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation. Clin Endocrinol (Oxf). 2002 Aug. 57(2):215-21. [Medline].
Domenico S, Davies TF, Schlumberger MJ, Hay ID, Larsen PR. Williams Textbook of Endocrinology. Thyroid Physiology and Diagnostic Evaluation of Patients with Thyroid Disorders. 12th ed. Philadelphia: Saunders Company; 2011. chap 11.
Gregory A, Brent, Terry F, Davies, Melmed. Williams Textbook of Endocrinology. Hypothyroidism and Thyroiditis. 12th ed. Philadelphia, PA Saunders Company; 2011. chap 13.
Kim WG, Yoon JH, Kim WB, Kim TY, Kim EY, Kim JM. Change of serum antithyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2008 Dec. 93(12):4683-9. [Medline].
Spencer CA, Takeuchi M, Kazarosyan M, Wang CC, Guttler RB, Singer PA. Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 1998 Apr. 83(4):1121-7. [Medline].
Susan J. Mandel, P. Reed Larsen, Terry F. Textbook of Endocrinology. Davies Melmed: Williams. Thyrotoxicosis. 12th ed. Philadelphia, PA Saunders Company; 2011. chap 12.
Termote K, Decallonne B, Mombaerts I. The influence of prior hyperthyroidism on euthyroid graves’ ophthalmopathy. J Ophthalmol. 2014. 2014:426898. [Medline]. [Full Text].
Georges Elhomsy, MD, ECNU, FACE Assistant Professor of Medicine, University of Kansas School of Medicine-Wichita
Georges Elhomsy, MD, ECNU, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, Endocrine Society, The Obesity Society
Disclosure: Received income in an amount equal to or greater than $250 from: Corcept and Novo-nordisk .
George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society
Disclosure: Nothing to disclose.
Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital
Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology
Disclosure: Nothing to disclose.
Antithyroid Antibody
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