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Monitoring Thyroid Function
I have questions about monitoring thyroid function and adjusting thyroid medication dosages. I am wondering which of the thyroid tests are needed to appropriately monitor the effectiveness of thyroid medications.
I have seen doctors adjust the medication, or keep the same dosage, based on the triiodothyronine (T3) and thyroxine (T4) levels. I have seen cases of a low thyroid-stimulating hormone (TSH) level (as low as 0.01) in which no changes were made to the medication regimen, or a low TSH in combination with another abnormal measurement in which an increase in the medication was made. I have also seen liothyronine added to levothyroxine or “natural” thyroid hormone in cases of a low TSH.
I have also heard of patients being treated according to symptoms. It confuses me as to the appropriate way to monitor and treat hypothyroidism. Can you please provide some input? Thank you!
Q: What do we know that has good evidence to support clinical decision-making in the management of patients with thyroid dysfunction?
Here are some pearls gleaned from the available literature and practical clinical experience:
The TSH is the single best screening test for diagnosing and monitoring ongoing therapy for hypothyroidism and hyperthyroidism. It is also the most sensitive test for detecting mild thyroid dysfunction (eg, subclinical hypothyroidism or hyperthyroidism) when the free T4 and total T3 levels are still in the normal range. The American Association of Clinical Endocrinologists (AACE) recommends 0.3 to 3.0 mIU/mL as the appropriate normal range for TSH. In older adults, a TSH up to 5 mIU/mL may be normal, and it is normal for TSH to be suppressed in first-trimester pregnancy.
Use of free T4 and total T3 is helpful when you need to check the immediate response to therapy before the TSH has had a chance to respond. The TSH typically takes six to eight weeks to accurately reflect thyroid hormone status after a change in therapy. Therefore, if you need to assess your patient’s status prior to that point, measurement of the free T4 and total T3 would be most helpful.
A common scenario is following treatment of hyperthyroidism with methimazole. You can determine an appropriate response to therapy when you see the free T4 and total T3 levels returning to normal, even though the TSH will still be suppressed for quite some time. If you find either a low free T4 or total T3 level on methimazole therapy, you would reduce the dose even though the TSH is still suppressed, because these tests more accurately reflect the acute change in thyroid hormone status. The TSH helps you fine-tune therapy once the free T4 and total T3 levels are in the normal range.
Symptoms and labs often don’t match. A patient with a TSH of 100 may feel just fine, and another with a TSH of 6 may feel markedly symptomatic. What we should strive for is normalizing the TSH between 0.3 and 3.0. However, because of the varying sensitivity of patients, it may be appropriate to experiment with different doses if a patient still feels symptomatic—as long as the TSH remains in the normal range.
For example: If a patient has a TSH of 2.5 on 100 mg but still feels cold and fatigued, try raising the dose to 112 mg daily to get the TSH closer to 1.0. Reassess the patient’s symptoms and TSH in six weeks. If symptoms are better and the TSH is still in the normal range, continue with 112 mg. If no improvement is noted despite a TSH now in the low-normal range, go back to 100 mg, as symptoms don’t appear to be thyroid related.
There is insufficient evidence to support the use of liothyronine or “natural” thyroid hormone products (eg, Armour, Nature Thyroid) for the treatment of hypothyroidism. One small study treated patients for only five weeks with a combination of levothyroxine and liothyronine and found beneficial changes in mood in a subset of patients. However, these results have not been replicated in any other studies. Furthermore, liothyronine may be dangerous in individuals with angina or dysrhythmias of the heart.
Suppression of TSH is in general undesirable and has a potential for adverse effects on cardiac function (eg, cardiac hypertrophy, atrial fibrillation) and bone metabolism (eg, accelerated bone loss). However, there are a few exceptions, such as thyroid hormone replacement therapy after thyroidectomy for well-differentiated thyroid cancer.
Some providers have used levothyroxine therapy to achieve mild suppression of TSH in an attempt to suppress the growth of hypofunctioning thyroid nodules. However, large studies have failed to show a benefit to that strategy.
Since commercially available levothyroxine products may not be bioequivalent, it is recommended to stay with the same manufacturer when possible. Thyroid hormone absorption can be adversely affected by many drugs and supplements, including cholestyramine, ferrous sulfate, sucralfate, calcium, and antacids containing aluminum hydroxide. It is best to take levothyroxine on an empty stomach first thing in the morning and to separate consumption of interfering substances by at least a half-hour and ideally by three to four hours. Always assess patients for compliance with doses and screen for interfering substances prior to increasing the dose of levothyroxine for an elevated TSH.
Suggested Reading
AACE. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. www.aace.com/publications/guidelines. Accessed July 11, 2011.
I have questions about monitoring thyroid function and adjusting thyroid medication dosages. I am wondering which of the thyroid tests are needed to appropriately monitor the effectiveness of thyroid medications.
I have seen doctors adjust the medication, or keep the same dosage, based on the triiodothyronine (T3) and thyroxine (T4) levels. I have seen cases of a low thyroid-stimulating hormone (TSH) level (as low as 0.01) in which no changes were made to the medication regimen, or a low TSH in combination with another abnormal measurement in which an increase in the medication was made. I have also seen liothyronine added to levothyroxine or “natural” thyroid hormone in cases of a low TSH.
I have also heard of patients being treated according to symptoms. It confuses me as to the appropriate way to monitor and treat hypothyroidism. Can you please provide some input? Thank you!
Q: What do we know that has good evidence to support clinical decision-making in the management of patients with thyroid dysfunction?
Here are some pearls gleaned from the available literature and practical clinical experience:
The TSH is the single best screening test for diagnosing and monitoring ongoing therapy for hypothyroidism and hyperthyroidism. It is also the most sensitive test for detecting mild thyroid dysfunction (eg, subclinical hypothyroidism or hyperthyroidism) when the free T4 and total T3 levels are still in the normal range. The American Association of Clinical Endocrinologists (AACE) recommends 0.3 to 3.0 mIU/mL as the appropriate normal range for TSH. In older adults, a TSH up to 5 mIU/mL may be normal, and it is normal for TSH to be suppressed in first-trimester pregnancy.
Use of free T4 and total T3 is helpful when you need to check the immediate response to therapy before the TSH has had a chance to respond. The TSH typically takes six to eight weeks to accurately reflect thyroid hormone status after a change in therapy. Therefore, if you need to assess your patient’s status prior to that point, measurement of the free T4 and total T3 would be most helpful.
A common scenario is following treatment of hyperthyroidism with methimazole. You can determine an appropriate response to therapy when you see the free T4 and total T3 levels returning to normal, even though the TSH will still be suppressed for quite some time. If you find either a low free T4 or total T3 level on methimazole therapy, you would reduce the dose even though the TSH is still suppressed, because these tests more accurately reflect the acute change in thyroid hormone status. The TSH helps you fine-tune therapy once the free T4 and total T3 levels are in the normal range.
Symptoms and labs often don’t match. A patient with a TSH of 100 may feel just fine, and another with a TSH of 6 may feel markedly symptomatic. What we should strive for is normalizing the TSH between 0.3 and 3.0. However, because of the varying sensitivity of patients, it may be appropriate to experiment with different doses if a patient still feels symptomatic—as long as the TSH remains in the normal range.
For example: If a patient has a TSH of 2.5 on 100 mg but still feels cold and fatigued, try raising the dose to 112 mg daily to get the TSH closer to 1.0. Reassess the patient’s symptoms and TSH in six weeks. If symptoms are better and the TSH is still in the normal range, continue with 112 mg. If no improvement is noted despite a TSH now in the low-normal range, go back to 100 mg, as symptoms don’t appear to be thyroid related.
There is insufficient evidence to support the use of liothyronine or “natural” thyroid hormone products (eg, Armour, Nature Thyroid) for the treatment of hypothyroidism. One small study treated patients for only five weeks with a combination of levothyroxine and liothyronine and found beneficial changes in mood in a subset of patients. However, these results have not been replicated in any other studies. Furthermore, liothyronine may be dangerous in individuals with angina or dysrhythmias of the heart.
Suppression of TSH is in general undesirable and has a potential for adverse effects on cardiac function (eg, cardiac hypertrophy, atrial fibrillation) and bone metabolism (eg, accelerated bone loss). However, there are a few exceptions, such as thyroid hormone replacement therapy after thyroidectomy for well-differentiated thyroid cancer.
Some providers have used levothyroxine therapy to achieve mild suppression of TSH in an attempt to suppress the growth of hypofunctioning thyroid nodules. However, large studies have failed to show a benefit to that strategy.
Since commercially available levothyroxine products may not be bioequivalent, it is recommended to stay with the same manufacturer when possible. Thyroid hormone absorption can be adversely affected by many drugs and supplements, including cholestyramine, ferrous sulfate, sucralfate, calcium, and antacids containing aluminum hydroxide. It is best to take levothyroxine on an empty stomach first thing in the morning and to separate consumption of interfering substances by at least a half-hour and ideally by three to four hours. Always assess patients for compliance with doses and screen for interfering substances prior to increasing the dose of levothyroxine for an elevated TSH.
Suggested Reading
AACE. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. www.aace.com/publications/guidelines. Accessed July 11, 2011.
I have questions about monitoring thyroid function and adjusting thyroid medication dosages. I am wondering which of the thyroid tests are needed to appropriately monitor the effectiveness of thyroid medications.
I have seen doctors adjust the medication, or keep the same dosage, based on the triiodothyronine (T3) and thyroxine (T4) levels. I have seen cases of a low thyroid-stimulating hormone (TSH) level (as low as 0.01) in which no changes were made to the medication regimen, or a low TSH in combination with another abnormal measurement in which an increase in the medication was made. I have also seen liothyronine added to levothyroxine or “natural” thyroid hormone in cases of a low TSH.
I have also heard of patients being treated according to symptoms. It confuses me as to the appropriate way to monitor and treat hypothyroidism. Can you please provide some input? Thank you!
Q: What do we know that has good evidence to support clinical decision-making in the management of patients with thyroid dysfunction?
Here are some pearls gleaned from the available literature and practical clinical experience:
The TSH is the single best screening test for diagnosing and monitoring ongoing therapy for hypothyroidism and hyperthyroidism. It is also the most sensitive test for detecting mild thyroid dysfunction (eg, subclinical hypothyroidism or hyperthyroidism) when the free T4 and total T3 levels are still in the normal range. The American Association of Clinical Endocrinologists (AACE) recommends 0.3 to 3.0 mIU/mL as the appropriate normal range for TSH. In older adults, a TSH up to 5 mIU/mL may be normal, and it is normal for TSH to be suppressed in first-trimester pregnancy.
Use of free T4 and total T3 is helpful when you need to check the immediate response to therapy before the TSH has had a chance to respond. The TSH typically takes six to eight weeks to accurately reflect thyroid hormone status after a change in therapy. Therefore, if you need to assess your patient’s status prior to that point, measurement of the free T4 and total T3 would be most helpful.
A common scenario is following treatment of hyperthyroidism with methimazole. You can determine an appropriate response to therapy when you see the free T4 and total T3 levels returning to normal, even though the TSH will still be suppressed for quite some time. If you find either a low free T4 or total T3 level on methimazole therapy, you would reduce the dose even though the TSH is still suppressed, because these tests more accurately reflect the acute change in thyroid hormone status. The TSH helps you fine-tune therapy once the free T4 and total T3 levels are in the normal range.
Symptoms and labs often don’t match. A patient with a TSH of 100 may feel just fine, and another with a TSH of 6 may feel markedly symptomatic. What we should strive for is normalizing the TSH between 0.3 and 3.0. However, because of the varying sensitivity of patients, it may be appropriate to experiment with different doses if a patient still feels symptomatic—as long as the TSH remains in the normal range.
For example: If a patient has a TSH of 2.5 on 100 mg but still feels cold and fatigued, try raising the dose to 112 mg daily to get the TSH closer to 1.0. Reassess the patient’s symptoms and TSH in six weeks. If symptoms are better and the TSH is still in the normal range, continue with 112 mg. If no improvement is noted despite a TSH now in the low-normal range, go back to 100 mg, as symptoms don’t appear to be thyroid related.
There is insufficient evidence to support the use of liothyronine or “natural” thyroid hormone products (eg, Armour, Nature Thyroid) for the treatment of hypothyroidism. One small study treated patients for only five weeks with a combination of levothyroxine and liothyronine and found beneficial changes in mood in a subset of patients. However, these results have not been replicated in any other studies. Furthermore, liothyronine may be dangerous in individuals with angina or dysrhythmias of the heart.
Suppression of TSH is in general undesirable and has a potential for adverse effects on cardiac function (eg, cardiac hypertrophy, atrial fibrillation) and bone metabolism (eg, accelerated bone loss). However, there are a few exceptions, such as thyroid hormone replacement therapy after thyroidectomy for well-differentiated thyroid cancer.
Some providers have used levothyroxine therapy to achieve mild suppression of TSH in an attempt to suppress the growth of hypofunctioning thyroid nodules. However, large studies have failed to show a benefit to that strategy.
Since commercially available levothyroxine products may not be bioequivalent, it is recommended to stay with the same manufacturer when possible. Thyroid hormone absorption can be adversely affected by many drugs and supplements, including cholestyramine, ferrous sulfate, sucralfate, calcium, and antacids containing aluminum hydroxide. It is best to take levothyroxine on an empty stomach first thing in the morning and to separate consumption of interfering substances by at least a half-hour and ideally by three to four hours. Always assess patients for compliance with doses and screen for interfering substances prior to increasing the dose of levothyroxine for an elevated TSH.
Suggested Reading
AACE. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. www.aace.com/publications/guidelines. Accessed July 11, 2011.
Thyroid Nodules
Q: I often detect thyroid nodules in the course of a routine exam or as an incidental finding during diagnostic imaging. How commonly are these found in the general population?
Thyroid nodules are found on routine physical examination in 3% to 7% of patients. It is important to note that 50% of patients with one palpable nodule on physical exam will have additional nodules on ultrasonography.
Incidental finding of thyroid nodules has increased dramatically with the more frequent use of imaging in medicine (eg, carotid Doppler studies and chest/neck CT). The estimated prevalence of clinically undetected nodules in the general population, as detected by ultrasonography, is 20% to 76%. This wide variation results from technical and definitional issues.
Q: What tests should I order if I feel a thyroid nodule on examination or find one or more on a nonrelated imaging study?
All patients with a palpable or incidental thyroid nodule should undergo thyroid ultrasonography. A serum thyroid-stimulating hormone (TSH) is the best initial screening test for thyroid function. If the TSH is low, it raises suspicion for a hyperfunctioning nodule or gland; a free T4 (thyroxine) and total T3 (triiodothyronine) should follow. If hyperthyroidism is confirmed, a “hot nodule” should be considered. (See section on thyroid scintigraphy below.)
If the TSH is high, measurement of antithyroid peroxidase antibodies (TPOAb) is appropriate. Measurement of serum thyroglobulin is not usually required in the evaluation of thyroid nodules.
Factors that increase the risk for malignancy are: growing and/or fixed nodule; firm or hard consistency; cervical adenopathy; history of head and neck irradiation; family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC); age < 14 or > 70 years; male sex; and persistent dysphonia, dysphagia, or dyspnea.
Q: When should I order a thyroid uptake and scan (thyroid scintigraphy)?
Thyroid scintigraphy may be helpful primarily in patients with a low serum TSH to detect hot nodules. Based on the pattern of radionuclide uptake, nodules are classified as hyperfunctioning (“hot”), hypofunctioning (“cold”), or indeterminate (neither hot nor cold). Hot nodules are almost never malignancies. Cold and indeterminate nodules may be malignant in 3% to 15% of cases. If the TSH is high or normal, the nodules will likely be cold or indeterminate, which has little predictive value.
Q: When should I consider ordering a thyroid fine-needle aspiration (FNA)?
It was once commonly assumed that a finding of multiple nodules on ultrasonography represented a decreased risk for thyroid malignancy. However, it is now known that the risk for malignancy is similar for solitary nodules, nodules in multinodular glands, or nodules embedded in large goiters. Additionally, the risk for cancer in nodules that are palpable on exam and in clinically undetectable nodules found incidentally is very similar (5.0% to 6.4% vs 5.4% to 7.7%, respectively).
Ultrasonographic characteristics can help identify suspicious nodules. This can be helpful in a multinodular gland, from which the nodule(s) chosen for FNA should be the one(s) with the most suspicious characteristics—not necessarily the largest. FNA is typically done by ultrasonographic guidance for more accurate sampling.
Ultrasound findings that may indicate malignancy include: hypoechogenicity in a solid or complex nodule; microcalcifications; irregular margins; intranodular vascularity; rounded appearance; and shape of the nodule more tall (anteroposterior) than wide (transverse).
When two or more of the characteristics above are present, the risk for malignancy increases. Often, ultrasound reports do not include sufficient information on these characteristics. When unsure about a nodule, the clinician should consult the radiologist, who can review the films with him/her for the presence or absence of the above characteristics.
In general, FNA is recommended for:
• Nodules > 1.0 cm that are solid and hypoechoic
• Nodules of any size with ultrasound findings suggestive of extracapsular growth or metastatic cervical lymph nodes
• Nodules of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; increased calcitonin levels in the absence of interfering factors
• Nodules of diameter < 1.0 cm that have ultrasound findings associated with malignancy; the coexistence of two or more suspicious ultrasound criteria greatly increases the risk of thyroid cancer
• Nodules previously found benign by FNA cytology that have grown significantly or have new suspicious characteristics.
Conclusion
Thyroid ultrasonography is extremely helpful for classification of thyroid nodules based on characteristics that increase the likelihood of malignancy. TSH, thyroid antibody tests, and thyroid scintigraphy assess thyroid function. Serial ultrasonography can follow nodules found to be low-risk and suspicious nodules with benign FNA results. If significant changes occur, reaspiration or surgery should be considered.
Referral to an endocrinologist is strongly recommended when there is not a clear course of clinical action (eg, cells are atypical or follicular neoplasm cannot be excluded) or a diagnosis of thyroid cancer is suspected. Excellent guidelines for the management of thyroid nodules can be found on the American Association of Clinical Endocrinologists Web site (https://www.aace.com/files/thyroid-guidelines.pdf).
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Q: I often detect thyroid nodules in the course of a routine exam or as an incidental finding during diagnostic imaging. How commonly are these found in the general population?
Thyroid nodules are found on routine physical examination in 3% to 7% of patients. It is important to note that 50% of patients with one palpable nodule on physical exam will have additional nodules on ultrasonography.
Incidental finding of thyroid nodules has increased dramatically with the more frequent use of imaging in medicine (eg, carotid Doppler studies and chest/neck CT). The estimated prevalence of clinically undetected nodules in the general population, as detected by ultrasonography, is 20% to 76%. This wide variation results from technical and definitional issues.
Q: What tests should I order if I feel a thyroid nodule on examination or find one or more on a nonrelated imaging study?
All patients with a palpable or incidental thyroid nodule should undergo thyroid ultrasonography. A serum thyroid-stimulating hormone (TSH) is the best initial screening test for thyroid function. If the TSH is low, it raises suspicion for a hyperfunctioning nodule or gland; a free T4 (thyroxine) and total T3 (triiodothyronine) should follow. If hyperthyroidism is confirmed, a “hot nodule” should be considered. (See section on thyroid scintigraphy below.)
If the TSH is high, measurement of antithyroid peroxidase antibodies (TPOAb) is appropriate. Measurement of serum thyroglobulin is not usually required in the evaluation of thyroid nodules.
Factors that increase the risk for malignancy are: growing and/or fixed nodule; firm or hard consistency; cervical adenopathy; history of head and neck irradiation; family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC); age < 14 or > 70 years; male sex; and persistent dysphonia, dysphagia, or dyspnea.
Q: When should I order a thyroid uptake and scan (thyroid scintigraphy)?
Thyroid scintigraphy may be helpful primarily in patients with a low serum TSH to detect hot nodules. Based on the pattern of radionuclide uptake, nodules are classified as hyperfunctioning (“hot”), hypofunctioning (“cold”), or indeterminate (neither hot nor cold). Hot nodules are almost never malignancies. Cold and indeterminate nodules may be malignant in 3% to 15% of cases. If the TSH is high or normal, the nodules will likely be cold or indeterminate, which has little predictive value.
Q: When should I consider ordering a thyroid fine-needle aspiration (FNA)?
It was once commonly assumed that a finding of multiple nodules on ultrasonography represented a decreased risk for thyroid malignancy. However, it is now known that the risk for malignancy is similar for solitary nodules, nodules in multinodular glands, or nodules embedded in large goiters. Additionally, the risk for cancer in nodules that are palpable on exam and in clinically undetectable nodules found incidentally is very similar (5.0% to 6.4% vs 5.4% to 7.7%, respectively).
Ultrasonographic characteristics can help identify suspicious nodules. This can be helpful in a multinodular gland, from which the nodule(s) chosen for FNA should be the one(s) with the most suspicious characteristics—not necessarily the largest. FNA is typically done by ultrasonographic guidance for more accurate sampling.
Ultrasound findings that may indicate malignancy include: hypoechogenicity in a solid or complex nodule; microcalcifications; irregular margins; intranodular vascularity; rounded appearance; and shape of the nodule more tall (anteroposterior) than wide (transverse).
When two or more of the characteristics above are present, the risk for malignancy increases. Often, ultrasound reports do not include sufficient information on these characteristics. When unsure about a nodule, the clinician should consult the radiologist, who can review the films with him/her for the presence or absence of the above characteristics.
In general, FNA is recommended for:
• Nodules > 1.0 cm that are solid and hypoechoic
• Nodules of any size with ultrasound findings suggestive of extracapsular growth or metastatic cervical lymph nodes
• Nodules of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; increased calcitonin levels in the absence of interfering factors
• Nodules of diameter < 1.0 cm that have ultrasound findings associated with malignancy; the coexistence of two or more suspicious ultrasound criteria greatly increases the risk of thyroid cancer
• Nodules previously found benign by FNA cytology that have grown significantly or have new suspicious characteristics.
Conclusion
Thyroid ultrasonography is extremely helpful for classification of thyroid nodules based on characteristics that increase the likelihood of malignancy. TSH, thyroid antibody tests, and thyroid scintigraphy assess thyroid function. Serial ultrasonography can follow nodules found to be low-risk and suspicious nodules with benign FNA results. If significant changes occur, reaspiration or surgery should be considered.
Referral to an endocrinologist is strongly recommended when there is not a clear course of clinical action (eg, cells are atypical or follicular neoplasm cannot be excluded) or a diagnosis of thyroid cancer is suspected. Excellent guidelines for the management of thyroid nodules can be found on the American Association of Clinical Endocrinologists Web site (https://www.aace.com/files/thyroid-guidelines.pdf).
Q: I often detect thyroid nodules in the course of a routine exam or as an incidental finding during diagnostic imaging. How commonly are these found in the general population?
Thyroid nodules are found on routine physical examination in 3% to 7% of patients. It is important to note that 50% of patients with one palpable nodule on physical exam will have additional nodules on ultrasonography.
Incidental finding of thyroid nodules has increased dramatically with the more frequent use of imaging in medicine (eg, carotid Doppler studies and chest/neck CT). The estimated prevalence of clinically undetected nodules in the general population, as detected by ultrasonography, is 20% to 76%. This wide variation results from technical and definitional issues.
Q: What tests should I order if I feel a thyroid nodule on examination or find one or more on a nonrelated imaging study?
All patients with a palpable or incidental thyroid nodule should undergo thyroid ultrasonography. A serum thyroid-stimulating hormone (TSH) is the best initial screening test for thyroid function. If the TSH is low, it raises suspicion for a hyperfunctioning nodule or gland; a free T4 (thyroxine) and total T3 (triiodothyronine) should follow. If hyperthyroidism is confirmed, a “hot nodule” should be considered. (See section on thyroid scintigraphy below.)
If the TSH is high, measurement of antithyroid peroxidase antibodies (TPOAb) is appropriate. Measurement of serum thyroglobulin is not usually required in the evaluation of thyroid nodules.
Factors that increase the risk for malignancy are: growing and/or fixed nodule; firm or hard consistency; cervical adenopathy; history of head and neck irradiation; family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC); age < 14 or > 70 years; male sex; and persistent dysphonia, dysphagia, or dyspnea.
Q: When should I order a thyroid uptake and scan (thyroid scintigraphy)?
Thyroid scintigraphy may be helpful primarily in patients with a low serum TSH to detect hot nodules. Based on the pattern of radionuclide uptake, nodules are classified as hyperfunctioning (“hot”), hypofunctioning (“cold”), or indeterminate (neither hot nor cold). Hot nodules are almost never malignancies. Cold and indeterminate nodules may be malignant in 3% to 15% of cases. If the TSH is high or normal, the nodules will likely be cold or indeterminate, which has little predictive value.
Q: When should I consider ordering a thyroid fine-needle aspiration (FNA)?
It was once commonly assumed that a finding of multiple nodules on ultrasonography represented a decreased risk for thyroid malignancy. However, it is now known that the risk for malignancy is similar for solitary nodules, nodules in multinodular glands, or nodules embedded in large goiters. Additionally, the risk for cancer in nodules that are palpable on exam and in clinically undetectable nodules found incidentally is very similar (5.0% to 6.4% vs 5.4% to 7.7%, respectively).
Ultrasonographic characteristics can help identify suspicious nodules. This can be helpful in a multinodular gland, from which the nodule(s) chosen for FNA should be the one(s) with the most suspicious characteristics—not necessarily the largest. FNA is typically done by ultrasonographic guidance for more accurate sampling.
Ultrasound findings that may indicate malignancy include: hypoechogenicity in a solid or complex nodule; microcalcifications; irregular margins; intranodular vascularity; rounded appearance; and shape of the nodule more tall (anteroposterior) than wide (transverse).
When two or more of the characteristics above are present, the risk for malignancy increases. Often, ultrasound reports do not include sufficient information on these characteristics. When unsure about a nodule, the clinician should consult the radiologist, who can review the films with him/her for the presence or absence of the above characteristics.
In general, FNA is recommended for:
• Nodules > 1.0 cm that are solid and hypoechoic
• Nodules of any size with ultrasound findings suggestive of extracapsular growth or metastatic cervical lymph nodes
• Nodules of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; increased calcitonin levels in the absence of interfering factors
• Nodules of diameter < 1.0 cm that have ultrasound findings associated with malignancy; the coexistence of two or more suspicious ultrasound criteria greatly increases the risk of thyroid cancer
• Nodules previously found benign by FNA cytology that have grown significantly or have new suspicious characteristics.
Conclusion
Thyroid ultrasonography is extremely helpful for classification of thyroid nodules based on characteristics that increase the likelihood of malignancy. TSH, thyroid antibody tests, and thyroid scintigraphy assess thyroid function. Serial ultrasonography can follow nodules found to be low-risk and suspicious nodules with benign FNA results. If significant changes occur, reaspiration or surgery should be considered.
Referral to an endocrinologist is strongly recommended when there is not a clear course of clinical action (eg, cells are atypical or follicular neoplasm cannot be excluded) or a diagnosis of thyroid cancer is suspected. Excellent guidelines for the management of thyroid nodules can be found on the American Association of Clinical Endocrinologists Web site (https://www.aace.com/files/thyroid-guidelines.pdf).