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How useful are autoantibodies in diagnosing thyroid disorders?
They’re useful in diagnosing Graves’ disease and, to a lesser extent, autoimmune thyroid disease; they can also help predict hypothyroidism. thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves’ disease by a moderate to large degree (strength of recommendation [SOR]: B, cross-sectional study). A positive or negative thyroid peroxidase antibody (TPOAb) test increases or decreases the probability of autoimmune thyroid disease by only a small to moderate degree (SOR: B, 3 cross-sectional studies).
Thyroid-stimulating hormone (TSH) levels >2 mU/L, although still in the normal range, can be followed up with TPOAb testing to determine whether the patient has an increased probability of developing hypothyroidism (SOR: B, cohort study with a vague hypothyroidism reference standard).
Evidence summary
Although TSH followed by free T4 remain the initial screening tests for thyroid disorders, adding thyroid autoantibodies may refine the diagnosis. Three principal thyroid antibodies—TPOAb, thyroglobulin, and TRAb—can be positive in a variety of autoimmune thyroid disorders. TPOAb represents a specific antigen of antimicrosomal antibody (AMA). It has largely replaced AMA testing in most laboratories and clinical settings.
Antibodies point to Graves’, autoimmune disorders
A cross-sectional study of 267 Singaporean patients with previously diagnosed thyroid disorders measured TRAb, AMA, and thyroglobulin (TABLE). TRAb levels >10 U/L were found to have a positive likelihood ratio (LR+) of 13 and a negative likelihood ratio (LR–) of 0.2 for Graves’ disease.1
Two cross-sectional studies compared AMA to TPOAb in healthy patients and those with autoimmune thyroid and nonthyroid disorders. One study of 235 people in a university endocrinology department found that a TPOAb level >190 U/mL yielded an LR+ of 10.75 and an LR– of 0.15 for chronic autoimmune (Hashimoto’s) thyroiditis [CAHT]; the AMA-positive sera yielded an LR+ of 13.67 and an LR– of 0.19. Both TPOAb and AMA test characteristics were highly associated with CAHT (P<.001).
TABLE
Autoimmune markers in thyroid disorders
| % TRA b >3.4 U/L | % TRA b >10 U/L | % AMA positive | % thyroglobulin positive | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Thyroid disorders | % of study patie nts | LR + | LR – | LR + | LR – | LR + | LR – | LR + | LR – |
| Graves’ disease | 68 | 4.6 | 0.1 | 13 | 0.2 | 1.3 | 0.6 | 1.1 | 0.9 |
| CAHT | 20 | 0.2 | 4.7 | 0.1 | 2.8 | 1.4 | 0.2 | 1.4 | 0.6 |
| Subacute thyroiditis | 4 | 0.2 | 3.0 | 0 | 2.4 | 0.1 | 3.6 | 0.5 | 1.5 |
| Thyroid nodules | 6 | 0.2 | 3.4 | 0 | 2.4 | 0.1 | 4.1 | 0.1 | 2.0 |
| Others | 2 | 0.8 | 1.4 | 0 | 2.3 | 0 | 2.8 | 0 | 2.0 |
| AMA, antimicrosomal antibodies; CAHT, chronic autoimmune (Hashimoto’s) thyroiditis; LR +, positive likelihood ratio; LR –, negative likelihood ratio; TRAb, thyrotropin receptor antibodies | |||||||||
| Source: Khoo DHC, et al.1 | |||||||||
TPOAb is more sensitive than AMA and thyroglobulin
In the second study comparing AMA to TPOAb, the thyroid antibody test results of 32 healthy patients were compared with those of 262 clinic patients. In those with known thyroid dysfunction, TPOAb was found to be a more sensitive assay than AMA for autoimmune thyroid disorders. The sensitivity of TPOAb levels >3.1 U/mL was 88.1%; AMA sensitivity was 70.2% (P<.001).2,3
A cross-sectional study (National Health and Nutrition Examination Survey [NHANES III]) evaluated the presence of thyroid antibodies in 17,353 people representing the geographic and ethnic distribution of the United States, 95% of whom were categorized as free of thyroid disease.4 The study found that TPOAb was more sensitive than thyroglobulin for diagnosing nonspecific thyroid disease. The diagnosis of thyroid disease was based on abnormal TSH and free T4 levels. Abnormally high levels of TPOAb had an LR+ of 4.3 and LR– of 0.6 (P<.0001) for thyroid disease, compared with an LR+ of 3.4 and LR– of 0.7 (P<.01) for abnormally elevated thyroglobulin.
TSH + TPOAb more accurate than TSH in women
In the early 1970s, a cohort study of 2779 adults from Great Britain attempted to establish the incidence of thyroid disease in the general population by measuring TSH and TPOAb. Twenty years later, investigators restudied 1708 people from the original sample to determine the incidence of hypothyroidism and the prognostic value of these 2 biochemical markers for its development. At follow-up, the definition of a new case of hypothyroidism was based on an “intention to treat by the general practitioner by meeting clear biochemical criteria and/or symptoms.”
The initial presence of abnormally high serum TPOAb levels and TSH >2.0 mU/L predicted a 4.3% annual risk of developing hypothyroidism compared with a 2.6% annual risk with serum TSH >6.0 mU/L alone in women. This risk was not estimated for men because of the small number of cases.5
Recommendations
The American Association of Clinical Endocrinologists (AACE) makes no specific recommendations about laboratory testing of thyroid antibodies. Based on clinical judgment, the AACE states that antibodies may be considered in the workup of hyperthyroidism and hypothyroidism and to determine potential risk to the fetus in pregnant women diagnosed with Graves’ disease.6
The National Academy of Clinical Biochemistry (NACB) recommends TPOAb measurements in patients who have Down syndrome, are pregnant, or have miscarried or failed in vitro fertilization. The NACB also advocates measuring TPOAb before treatment with amiodarone, lithium, interferon-α, or interleukin-2.7
1. Khoo DHC, Fok ACK, Tan CE, et al. Thyroid stimulating hormone receptor antibody levels in Singaporean patients with autoimmune thyroid disease. Ann Acad Med Singapore. 1997;26:435-438.
2. Feldt-Rasmussen U, Hoier-Madsen M, Bech K, et al. Antithyroid peroxidase antibodies in thyroid disorders and nonthyroid autoimmune diseases. Autoimmunity. 1991;9:245-254.
3. Doullay F, Ruf J, Codaccioni JL, Carayon P. Prevalence of autoantibodies to thyroperoxidase in patients with various thyroid and autoimmune diseases. Autoimmunity. 1991;9:237-244.
4. Hollowell JG, Staehling NW, Flanders WD, et al. Srum TSH, T4, and thyroid antibodies in the united states population (1998 to 1994): National Health and Nutrition Examination Survey (NHANES III.) J Clin Endocrinol Metab. 2002;87:489-499.
5. Vanderpump MPJ, Tunbridge WMG, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow up of the Whickham survey. Clin Endocrinol (Oxf). 1995;43:55-68.
6. American Association of Clinical Endocrinologists Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Available at: www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf. Accessed June 8, 2007.
7. Demers LM, Spencer CA. Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Washington, DC: AACC press; 2003.
They’re useful in diagnosing Graves’ disease and, to a lesser extent, autoimmune thyroid disease; they can also help predict hypothyroidism. thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves’ disease by a moderate to large degree (strength of recommendation [SOR]: B, cross-sectional study). A positive or negative thyroid peroxidase antibody (TPOAb) test increases or decreases the probability of autoimmune thyroid disease by only a small to moderate degree (SOR: B, 3 cross-sectional studies).
Thyroid-stimulating hormone (TSH) levels >2 mU/L, although still in the normal range, can be followed up with TPOAb testing to determine whether the patient has an increased probability of developing hypothyroidism (SOR: B, cohort study with a vague hypothyroidism reference standard).
Evidence summary
Although TSH followed by free T4 remain the initial screening tests for thyroid disorders, adding thyroid autoantibodies may refine the diagnosis. Three principal thyroid antibodies—TPOAb, thyroglobulin, and TRAb—can be positive in a variety of autoimmune thyroid disorders. TPOAb represents a specific antigen of antimicrosomal antibody (AMA). It has largely replaced AMA testing in most laboratories and clinical settings.
Antibodies point to Graves’, autoimmune disorders
A cross-sectional study of 267 Singaporean patients with previously diagnosed thyroid disorders measured TRAb, AMA, and thyroglobulin (TABLE). TRAb levels >10 U/L were found to have a positive likelihood ratio (LR+) of 13 and a negative likelihood ratio (LR–) of 0.2 for Graves’ disease.1
Two cross-sectional studies compared AMA to TPOAb in healthy patients and those with autoimmune thyroid and nonthyroid disorders. One study of 235 people in a university endocrinology department found that a TPOAb level >190 U/mL yielded an LR+ of 10.75 and an LR– of 0.15 for chronic autoimmune (Hashimoto’s) thyroiditis [CAHT]; the AMA-positive sera yielded an LR+ of 13.67 and an LR– of 0.19. Both TPOAb and AMA test characteristics were highly associated with CAHT (P<.001).
TABLE
Autoimmune markers in thyroid disorders
| % TRA b >3.4 U/L | % TRA b >10 U/L | % AMA positive | % thyroglobulin positive | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Thyroid disorders | % of study patie nts | LR + | LR – | LR + | LR – | LR + | LR – | LR + | LR – |
| Graves’ disease | 68 | 4.6 | 0.1 | 13 | 0.2 | 1.3 | 0.6 | 1.1 | 0.9 |
| CAHT | 20 | 0.2 | 4.7 | 0.1 | 2.8 | 1.4 | 0.2 | 1.4 | 0.6 |
| Subacute thyroiditis | 4 | 0.2 | 3.0 | 0 | 2.4 | 0.1 | 3.6 | 0.5 | 1.5 |
| Thyroid nodules | 6 | 0.2 | 3.4 | 0 | 2.4 | 0.1 | 4.1 | 0.1 | 2.0 |
| Others | 2 | 0.8 | 1.4 | 0 | 2.3 | 0 | 2.8 | 0 | 2.0 |
| AMA, antimicrosomal antibodies; CAHT, chronic autoimmune (Hashimoto’s) thyroiditis; LR +, positive likelihood ratio; LR –, negative likelihood ratio; TRAb, thyrotropin receptor antibodies | |||||||||
| Source: Khoo DHC, et al.1 | |||||||||
TPOAb is more sensitive than AMA and thyroglobulin
In the second study comparing AMA to TPOAb, the thyroid antibody test results of 32 healthy patients were compared with those of 262 clinic patients. In those with known thyroid dysfunction, TPOAb was found to be a more sensitive assay than AMA for autoimmune thyroid disorders. The sensitivity of TPOAb levels >3.1 U/mL was 88.1%; AMA sensitivity was 70.2% (P<.001).2,3
A cross-sectional study (National Health and Nutrition Examination Survey [NHANES III]) evaluated the presence of thyroid antibodies in 17,353 people representing the geographic and ethnic distribution of the United States, 95% of whom were categorized as free of thyroid disease.4 The study found that TPOAb was more sensitive than thyroglobulin for diagnosing nonspecific thyroid disease. The diagnosis of thyroid disease was based on abnormal TSH and free T4 levels. Abnormally high levels of TPOAb had an LR+ of 4.3 and LR– of 0.6 (P<.0001) for thyroid disease, compared with an LR+ of 3.4 and LR– of 0.7 (P<.01) for abnormally elevated thyroglobulin.
TSH + TPOAb more accurate than TSH in women
In the early 1970s, a cohort study of 2779 adults from Great Britain attempted to establish the incidence of thyroid disease in the general population by measuring TSH and TPOAb. Twenty years later, investigators restudied 1708 people from the original sample to determine the incidence of hypothyroidism and the prognostic value of these 2 biochemical markers for its development. At follow-up, the definition of a new case of hypothyroidism was based on an “intention to treat by the general practitioner by meeting clear biochemical criteria and/or symptoms.”
The initial presence of abnormally high serum TPOAb levels and TSH >2.0 mU/L predicted a 4.3% annual risk of developing hypothyroidism compared with a 2.6% annual risk with serum TSH >6.0 mU/L alone in women. This risk was not estimated for men because of the small number of cases.5
Recommendations
The American Association of Clinical Endocrinologists (AACE) makes no specific recommendations about laboratory testing of thyroid antibodies. Based on clinical judgment, the AACE states that antibodies may be considered in the workup of hyperthyroidism and hypothyroidism and to determine potential risk to the fetus in pregnant women diagnosed with Graves’ disease.6
The National Academy of Clinical Biochemistry (NACB) recommends TPOAb measurements in patients who have Down syndrome, are pregnant, or have miscarried or failed in vitro fertilization. The NACB also advocates measuring TPOAb before treatment with amiodarone, lithium, interferon-α, or interleukin-2.7
They’re useful in diagnosing Graves’ disease and, to a lesser extent, autoimmune thyroid disease; they can also help predict hypothyroidism. thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves’ disease by a moderate to large degree (strength of recommendation [SOR]: B, cross-sectional study). A positive or negative thyroid peroxidase antibody (TPOAb) test increases or decreases the probability of autoimmune thyroid disease by only a small to moderate degree (SOR: B, 3 cross-sectional studies).
Thyroid-stimulating hormone (TSH) levels >2 mU/L, although still in the normal range, can be followed up with TPOAb testing to determine whether the patient has an increased probability of developing hypothyroidism (SOR: B, cohort study with a vague hypothyroidism reference standard).
Evidence summary
Although TSH followed by free T4 remain the initial screening tests for thyroid disorders, adding thyroid autoantibodies may refine the diagnosis. Three principal thyroid antibodies—TPOAb, thyroglobulin, and TRAb—can be positive in a variety of autoimmune thyroid disorders. TPOAb represents a specific antigen of antimicrosomal antibody (AMA). It has largely replaced AMA testing in most laboratories and clinical settings.
Antibodies point to Graves’, autoimmune disorders
A cross-sectional study of 267 Singaporean patients with previously diagnosed thyroid disorders measured TRAb, AMA, and thyroglobulin (TABLE). TRAb levels >10 U/L were found to have a positive likelihood ratio (LR+) of 13 and a negative likelihood ratio (LR–) of 0.2 for Graves’ disease.1
Two cross-sectional studies compared AMA to TPOAb in healthy patients and those with autoimmune thyroid and nonthyroid disorders. One study of 235 people in a university endocrinology department found that a TPOAb level >190 U/mL yielded an LR+ of 10.75 and an LR– of 0.15 for chronic autoimmune (Hashimoto’s) thyroiditis [CAHT]; the AMA-positive sera yielded an LR+ of 13.67 and an LR– of 0.19. Both TPOAb and AMA test characteristics were highly associated with CAHT (P<.001).
TABLE
Autoimmune markers in thyroid disorders
| % TRA b >3.4 U/L | % TRA b >10 U/L | % AMA positive | % thyroglobulin positive | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Thyroid disorders | % of study patie nts | LR + | LR – | LR + | LR – | LR + | LR – | LR + | LR – |
| Graves’ disease | 68 | 4.6 | 0.1 | 13 | 0.2 | 1.3 | 0.6 | 1.1 | 0.9 |
| CAHT | 20 | 0.2 | 4.7 | 0.1 | 2.8 | 1.4 | 0.2 | 1.4 | 0.6 |
| Subacute thyroiditis | 4 | 0.2 | 3.0 | 0 | 2.4 | 0.1 | 3.6 | 0.5 | 1.5 |
| Thyroid nodules | 6 | 0.2 | 3.4 | 0 | 2.4 | 0.1 | 4.1 | 0.1 | 2.0 |
| Others | 2 | 0.8 | 1.4 | 0 | 2.3 | 0 | 2.8 | 0 | 2.0 |
| AMA, antimicrosomal antibodies; CAHT, chronic autoimmune (Hashimoto’s) thyroiditis; LR +, positive likelihood ratio; LR –, negative likelihood ratio; TRAb, thyrotropin receptor antibodies | |||||||||
| Source: Khoo DHC, et al.1 | |||||||||
TPOAb is more sensitive than AMA and thyroglobulin
In the second study comparing AMA to TPOAb, the thyroid antibody test results of 32 healthy patients were compared with those of 262 clinic patients. In those with known thyroid dysfunction, TPOAb was found to be a more sensitive assay than AMA for autoimmune thyroid disorders. The sensitivity of TPOAb levels >3.1 U/mL was 88.1%; AMA sensitivity was 70.2% (P<.001).2,3
A cross-sectional study (National Health and Nutrition Examination Survey [NHANES III]) evaluated the presence of thyroid antibodies in 17,353 people representing the geographic and ethnic distribution of the United States, 95% of whom were categorized as free of thyroid disease.4 The study found that TPOAb was more sensitive than thyroglobulin for diagnosing nonspecific thyroid disease. The diagnosis of thyroid disease was based on abnormal TSH and free T4 levels. Abnormally high levels of TPOAb had an LR+ of 4.3 and LR– of 0.6 (P<.0001) for thyroid disease, compared with an LR+ of 3.4 and LR– of 0.7 (P<.01) for abnormally elevated thyroglobulin.
TSH + TPOAb more accurate than TSH in women
In the early 1970s, a cohort study of 2779 adults from Great Britain attempted to establish the incidence of thyroid disease in the general population by measuring TSH and TPOAb. Twenty years later, investigators restudied 1708 people from the original sample to determine the incidence of hypothyroidism and the prognostic value of these 2 biochemical markers for its development. At follow-up, the definition of a new case of hypothyroidism was based on an “intention to treat by the general practitioner by meeting clear biochemical criteria and/or symptoms.”
The initial presence of abnormally high serum TPOAb levels and TSH >2.0 mU/L predicted a 4.3% annual risk of developing hypothyroidism compared with a 2.6% annual risk with serum TSH >6.0 mU/L alone in women. This risk was not estimated for men because of the small number of cases.5
Recommendations
The American Association of Clinical Endocrinologists (AACE) makes no specific recommendations about laboratory testing of thyroid antibodies. Based on clinical judgment, the AACE states that antibodies may be considered in the workup of hyperthyroidism and hypothyroidism and to determine potential risk to the fetus in pregnant women diagnosed with Graves’ disease.6
The National Academy of Clinical Biochemistry (NACB) recommends TPOAb measurements in patients who have Down syndrome, are pregnant, or have miscarried or failed in vitro fertilization. The NACB also advocates measuring TPOAb before treatment with amiodarone, lithium, interferon-α, or interleukin-2.7
1. Khoo DHC, Fok ACK, Tan CE, et al. Thyroid stimulating hormone receptor antibody levels in Singaporean patients with autoimmune thyroid disease. Ann Acad Med Singapore. 1997;26:435-438.
2. Feldt-Rasmussen U, Hoier-Madsen M, Bech K, et al. Antithyroid peroxidase antibodies in thyroid disorders and nonthyroid autoimmune diseases. Autoimmunity. 1991;9:245-254.
3. Doullay F, Ruf J, Codaccioni JL, Carayon P. Prevalence of autoantibodies to thyroperoxidase in patients with various thyroid and autoimmune diseases. Autoimmunity. 1991;9:237-244.
4. Hollowell JG, Staehling NW, Flanders WD, et al. Srum TSH, T4, and thyroid antibodies in the united states population (1998 to 1994): National Health and Nutrition Examination Survey (NHANES III.) J Clin Endocrinol Metab. 2002;87:489-499.
5. Vanderpump MPJ, Tunbridge WMG, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow up of the Whickham survey. Clin Endocrinol (Oxf). 1995;43:55-68.
6. American Association of Clinical Endocrinologists Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Available at: www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf. Accessed June 8, 2007.
7. Demers LM, Spencer CA. Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Washington, DC: AACC press; 2003.
1. Khoo DHC, Fok ACK, Tan CE, et al. Thyroid stimulating hormone receptor antibody levels in Singaporean patients with autoimmune thyroid disease. Ann Acad Med Singapore. 1997;26:435-438.
2. Feldt-Rasmussen U, Hoier-Madsen M, Bech K, et al. Antithyroid peroxidase antibodies in thyroid disorders and nonthyroid autoimmune diseases. Autoimmunity. 1991;9:245-254.
3. Doullay F, Ruf J, Codaccioni JL, Carayon P. Prevalence of autoantibodies to thyroperoxidase in patients with various thyroid and autoimmune diseases. Autoimmunity. 1991;9:237-244.
4. Hollowell JG, Staehling NW, Flanders WD, et al. Srum TSH, T4, and thyroid antibodies in the united states population (1998 to 1994): National Health and Nutrition Examination Survey (NHANES III.) J Clin Endocrinol Metab. 2002;87:489-499.
5. Vanderpump MPJ, Tunbridge WMG, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow up of the Whickham survey. Clin Endocrinol (Oxf). 1995;43:55-68.
6. American Association of Clinical Endocrinologists Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Available at: www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf. Accessed June 8, 2007.
7. Demers LM, Spencer CA. Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease. Washington, DC: AACC press; 2003.
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