Thyroid Peroxidase Antibodies

Q: I have a patient with premature ovarian failure (diagnosed when she was 32) who is now in her late 40s. She is fatigued, and a blood test revealed a thyroid peroxidase antibodies level of 587 IU/mL. Would you supplement with thyroid replacement hormone, even though she has a TSH of 1.004?

The short answer is: No. Thyroid peroxidase (TPO) antibodies are a marker for the presence of autoimmune thyroid disease. Blood test results for TPO antibodies are positive in 95% of patients with chronic lymphocytic thyroiditis, also known as Hashimoto’s disease, and in 50% to 80% of patients with Graves’ disease. 

Patients with high levels of TPO antibodies are at risk for future thyroid dysfunction. Not all patients with Hashimoto’s develop hypothyroidism, and if present, it may not persist. Patients with Hashimoto’s, although rarely, can experience a change from a hypothyroid to a euthyroid or even a hyperthyroid state, because of the development of coexisting TSH-receptor antibodies (TRAb), which include thyroid-stimulating immunoglobulin (TSI) and thyrotropin-binding inhibitory immunoglobulin (TBII), as seen in Graves’ disease.

Thyroid nodules are common with Hashimoto’s and are associated with a small risk (5% to 7%) for thyroid cancer. Sudden enlargement of the thyroid gland in a patient with Hashimoto’s should raise concern about thyroid lymphoma. Some endocrinologists will give supplemental thyroid hormone to a patient with Hashimoto’s, even if the TSH is normal, in an attempt to shrink the size of the gland. However, the closer the TSH is to < 1, the less room there is to further suppress it without making the patient overtly hyperthyroid, and the less likely it is that you will achieve much shrinkage of the gland. 

Therefore, in the absence of a symptomatic goiter, there is no clinical reason to initiate any therapy. Even with mildly elevated TSH levels (5 to 10 mIU/L; ie, subclinical hypothyroidism) in an asymptomatic patient, there is considerable controversy about thyroid hormone initiation when the free T4 and T3 levels are normal. Most authorities agree that treatment should be initiated in most patients when the TSH rises above 10 mIU/L, regardless of symptoms. However, there are clearer indications to start thyroid hormone in women who want to become, or who are, pregnant, to maintain a TSH of < 2.5 mIU/L. Also, individuals with depression or hyperlipidemia warrant extra consideration for the use of thyroid hormone.

Since this particular patient had premature ovarian failure, which is often autoimmune in nature, she must be considered at risk for future development of hypothyroidism. This patient should be followed annually to ensure that her TSH does not rise. Should she develop symptoms suggestive of hypothyroidism and her TSH rises above 3, some endocrinologists would initiate a brief empiric trial of thyroid replacement to see if her symptoms respond when the TSH lowers again. If they do not, the thyroid hormone might be stopped, and the patient should continue to be followed.

Note: The definition of a “normal” TSH is evolving. Levels above 3.0 (suggested normal therapeutic range: 0.5 to 3.0) are considered possibly suspicious in symptomatic young people, while levels slightly above the normal reference range (5 to 7 mIU/L) may be deemed normal for the asymptomatic geriatric population.

The other point to remember is that when a clinician initiates any thyroid therapy, some patients fixate on the thyroid as the only source of their symptoms, such as fatigue, weight gain, and obesity, to the exclusion of any other etiologies. For example, sleep deprivation is a far more common cause of fatigue in our “open 24 hours” society, and lifestyle remains the major cause of obesity. Thus, there can be unintended consequences of a diagnosis of thyroid “disease.”

SUGGESTED READING
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. www.aace.com/publications/guidelines. Accessed March 5, 2012.

Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab. 2012 Feb 16; [Epub ahead of print].

Hutfless S, Matos P, Talor MV, et al. Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. J Clin Endocrinol Metab. 2011;96(9):E1466-E1471.

Kauffman RP, Castracane VD. Premature ovarian failure associated with autoimmune polyglandular syndrome: pathophysiological mechanisms and future fertility. J Womens Health (Larchmt). 2003;12(5):513-520.

Q: I have a patient with premature ovarian failure (diagnosed when she was 32) who is now in her late 40s. She is fatigued, and a blood test revealed a thyroid peroxidase antibodies level of 587 IU/mL. Would you supplement with thyroid replacement hormone, even though she has a TSH of 1.004?

The short answer is: No. Thyroid peroxidase (TPO) antibodies are a marker for the presence of autoimmune thyroid disease. Blood test results for TPO antibodies are positive in 95% of patients with chronic lymphocytic thyroiditis, also known as Hashimoto’s disease, and in 50% to 80% of patients with Graves’ disease. 

Patients with high levels of TPO antibodies are at risk for future thyroid dysfunction. Not all patients with Hashimoto’s develop hypothyroidism, and if present, it may not persist. Patients with Hashimoto’s, although rarely, can experience a change from a hypothyroid to a euthyroid or even a hyperthyroid state, because of the development of coexisting TSH-receptor antibodies (TRAb), which include thyroid-stimulating immunoglobulin (TSI) and thyrotropin-binding inhibitory immunoglobulin (TBII), as seen in Graves’ disease.

Thyroid nodules are common with Hashimoto’s and are associated with a small risk (5% to 7%) for thyroid cancer. Sudden enlargement of the thyroid gland in a patient with Hashimoto’s should raise concern about thyroid lymphoma. Some endocrinologists will give supplemental thyroid hormone to a patient with Hashimoto’s, even if the TSH is normal, in an attempt to shrink the size of the gland. However, the closer the TSH is to < 1, the less room there is to further suppress it without making the patient overtly hyperthyroid, and the less likely it is that you will achieve much shrinkage of the gland. 

Therefore, in the absence of a symptomatic goiter, there is no clinical reason to initiate any therapy. Even with mildly elevated TSH levels (5 to 10 mIU/L; ie, subclinical hypothyroidism) in an asymptomatic patient, there is considerable controversy about thyroid hormone initiation when the free T4 and T3 levels are normal. Most authorities agree that treatment should be initiated in most patients when the TSH rises above 10 mIU/L, regardless of symptoms. However, there are clearer indications to start thyroid hormone in women who want to become, or who are, pregnant, to maintain a TSH of < 2.5 mIU/L. Also, individuals with depression or hyperlipidemia warrant extra consideration for the use of thyroid hormone.

Since this particular patient had premature ovarian failure, which is often autoimmune in nature, she must be considered at risk for future development of hypothyroidism. This patient should be followed annually to ensure that her TSH does not rise. Should she develop symptoms suggestive of hypothyroidism and her TSH rises above 3, some endocrinologists would initiate a brief empiric trial of thyroid replacement to see if her symptoms respond when the TSH lowers again. If they do not, the thyroid hormone might be stopped, and the patient should continue to be followed.

Note: The definition of a “normal” TSH is evolving. Levels above 3.0 (suggested normal therapeutic range: 0.5 to 3.0) are considered possibly suspicious in symptomatic young people, while levels slightly above the normal reference range (5 to 7 mIU/L) may be deemed normal for the asymptomatic geriatric population.

The other point to remember is that when a clinician initiates any thyroid therapy, some patients fixate on the thyroid as the only source of their symptoms, such as fatigue, weight gain, and obesity, to the exclusion of any other etiologies. For example, sleep deprivation is a far more common cause of fatigue in our “open 24 hours” society, and lifestyle remains the major cause of obesity. Thus, there can be unintended consequences of a diagnosis of thyroid “disease.”

SUGGESTED READING
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. www.aace.com/publications/guidelines. Accessed March 5, 2012.

Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab. 2012 Feb 16; [Epub ahead of print].

Hutfless S, Matos P, Talor MV, et al. Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. J Clin Endocrinol Metab. 2011;96(9):E1466-E1471.

Kauffman RP, Castracane VD. Premature ovarian failure associated with autoimmune polyglandular syndrome: pathophysiological mechanisms and future fertility. J Womens Health (Larchmt). 2003;12(5):513-520.

Q: I have a patient with premature ovarian failure (diagnosed when she was 32) who is now in her late 40s. She is fatigued, and a blood test revealed a thyroid peroxidase antibodies level of 587 IU/mL. Would you supplement with thyroid replacement hormone, even though she has a TSH of 1.004?

The short answer is: No. Thyroid peroxidase (TPO) antibodies are a marker for the presence of autoimmune thyroid disease. Blood test results for TPO antibodies are positive in 95% of patients with chronic lymphocytic thyroiditis, also known as Hashimoto’s disease, and in 50% to 80% of patients with Graves’ disease. 

Patients with high levels of TPO antibodies are at risk for future thyroid dysfunction. Not all patients with Hashimoto’s develop hypothyroidism, and if present, it may not persist. Patients with Hashimoto’s, although rarely, can experience a change from a hypothyroid to a euthyroid or even a hyperthyroid state, because of the development of coexisting TSH-receptor antibodies (TRAb), which include thyroid-stimulating immunoglobulin (TSI) and thyrotropin-binding inhibitory immunoglobulin (TBII), as seen in Graves’ disease.

Thyroid nodules are common with Hashimoto’s and are associated with a small risk (5% to 7%) for thyroid cancer. Sudden enlargement of the thyroid gland in a patient with Hashimoto’s should raise concern about thyroid lymphoma. Some endocrinologists will give supplemental thyroid hormone to a patient with Hashimoto’s, even if the TSH is normal, in an attempt to shrink the size of the gland. However, the closer the TSH is to < 1, the less room there is to further suppress it without making the patient overtly hyperthyroid, and the less likely it is that you will achieve much shrinkage of the gland. 

Therefore, in the absence of a symptomatic goiter, there is no clinical reason to initiate any therapy. Even with mildly elevated TSH levels (5 to 10 mIU/L; ie, subclinical hypothyroidism) in an asymptomatic patient, there is considerable controversy about thyroid hormone initiation when the free T4 and T3 levels are normal. Most authorities agree that treatment should be initiated in most patients when the TSH rises above 10 mIU/L, regardless of symptoms. However, there are clearer indications to start thyroid hormone in women who want to become, or who are, pregnant, to maintain a TSH of < 2.5 mIU/L. Also, individuals with depression or hyperlipidemia warrant extra consideration for the use of thyroid hormone.

Since this particular patient had premature ovarian failure, which is often autoimmune in nature, she must be considered at risk for future development of hypothyroidism. This patient should be followed annually to ensure that her TSH does not rise. Should she develop symptoms suggestive of hypothyroidism and her TSH rises above 3, some endocrinologists would initiate a brief empiric trial of thyroid replacement to see if her symptoms respond when the TSH lowers again. If they do not, the thyroid hormone might be stopped, and the patient should continue to be followed.

Note: The definition of a “normal” TSH is evolving. Levels above 3.0 (suggested normal therapeutic range: 0.5 to 3.0) are considered possibly suspicious in symptomatic young people, while levels slightly above the normal reference range (5 to 7 mIU/L) may be deemed normal for the asymptomatic geriatric population.

The other point to remember is that when a clinician initiates any thyroid therapy, some patients fixate on the thyroid as the only source of their symptoms, such as fatigue, weight gain, and obesity, to the exclusion of any other etiologies. For example, sleep deprivation is a far more common cause of fatigue in our “open 24 hours” society, and lifestyle remains the major cause of obesity. Thus, there can be unintended consequences of a diagnosis of thyroid “disease.”

SUGGESTED READING
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. www.aace.com/publications/guidelines. Accessed March 5, 2012.

Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab. 2012 Feb 16; [Epub ahead of print].

Hutfless S, Matos P, Talor MV, et al. Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. J Clin Endocrinol Metab. 2011;96(9):E1466-E1471.

Kauffman RP, Castracane VD. Premature ovarian failure associated with autoimmune polyglandular syndrome: pathophysiological mechanisms and future fertility. J Womens Health (Larchmt). 2003;12(5):513-520.