Tiroit nodüllerinin yönetiminde güncel kılavuzlar. (İng)

Current Guidelines for the Management of Thyroid Nodules

Robert A. Levine, MD, FACE, ECNU

Posted: 09/28/2012; Endocr Pract. 2012;18(4):596-599. © 2012 American Association of Clinical Endocrinologists

Abstract and Introduction

Introduction

Three sets of guidelines regarding management of thyroid nodules have been published during the past 3 years. The first set was issued by the American Thyroid Association (ATA),^[1] the second was by the American Association of Clinical Endocrinologists (AACE), in collaboration with the Associazione Medici Endocrinologi (AME) and the European Thyroid Association (ETA),^[2] and the most recent was by the Korean Society of Thyroid Radiology (KSTR).^[3] These guidelines have many similarities, but each set takes a slightly different approach to recommending which nodules should undergo biopsy.

Thyroid nodules are extremely common. An estimated 4% of the population have a palpable thyroid nodule, and more than 50% have a nodule detectable by ultrasonography. With the frequent use of computed tomographic scans and carotid ultrasound studies, many thyroid nodules are found in asymptomatic patients. In my practice, this has generated more than one-third of referrals for consultation regarding a thyroid nodule. Each of the guidelines addresses which nodules necessitate a biopsy and which can be safely monitored or ignored.

All of these guidelines are part of comprehensive articles, with numerous references and detailed discussions of the rationale behind the recommendations. Collectively, they encompass 105 pages, with more than 700 references. This brief commentary can provide only the highlights of the recommendations, and readers are encouraged to refer to the original articles for the background information, the details regarding the recommendations, and the strength of evidence supporting the recommendations.

ATA Guidelines

The ATA guidelines, revised in 2009, begin by asking whether the patient has a history suggestive of a high risk for thyroid cancer. Risk factors include radiation exposure during childhood, rapid growth of a nodule, hoarseness, vocal cord paralysis, dysphagia, or a family history of thyroid cancer or multiple endocrine neoplasia syndrome. If the patient has a high-risk history, the recommendation is to obtain a biopsy specimen from any thyroid nodule larger than 5 mm in diameter with suspicious features.

For patients without a high-risk history, the guidelines then ask whether abnormal cervical lymph nodes are present, detected by either physical examination or ultrasound study. If so, biopsy samples should be obtained from the lymph nodes themselves, with or without biopsy of any suspicious thyroid nodules present.

Microcalcifications have a high specificity for papillary cancer. Thus, biopsy is recommended for any nodule exhibiting microcalcifications and measuring more than 1 cm.

For those patients without a high-risk history, abnormal lymph nodes, or microcalcifications, the ATA guidelines then divide the thyroid nodules into categories on the basis of their composition. Nodules are characterized as entirely solid, mixed cystic-solid, spongiform, or purely cystic. Biopsy is recommended for all solid hypoechoic nodules that exceed 1 cm in diameter. Isoechoic or hyperechoic nodules exceeding 1 to 1.5 cm should undergo biopsy. Biopsy is recommended for mixed cystic-solid nodules that exceed 1.5 to 2 cm, if they have irregular margins, microcalcifications, or infiltration of the surrounding tissue. The recommendation for mixed cystic-solid nodules without suspicious ultrasonographic features is for biopsy if they are larger than 2 cm. Those nodules exhibiting a spongiform echotexture should undergo biopsy only if they are larger than 2 cm in diameter. Finally, purely cystic nodules do not require biopsy under the ATA guidelines.

AACE, AME, and ETA Guidelines

AACE, in collaboration with the AME and ETA, published guidelines for the diagnosis and management of thyroid nodules in 2010. They recommend biopsy of any solid and hypoechoic nodule larger than 1 cm in diameter. They further recommend that thyroid nodules of any size undergo biopsy if the patient has been exposed to irradiation, has a family history of medullary carcinoma or multiple endocrine neoplasia, or has previously undergone partial thyroidectomy for thyroid cancer or if an elevated calcitonin level is present. The AACE/AME/ETA guidelines recommend biopsy of nodules of any size with marked hypoechogenicity, irregular or microlobulated margins, a taller than wide configuration (anteroposterior dimension greater than transverse dimension), microcalcifications, or “chaotic arrangement of intranodular vascular images” or “chaotic intranodular vascular spots.” These guidelines recommend biopsy independent of size if ultrasonography suggests the presence of metastatic lymph nodes or if extracapsular growth is noted in the nodule. They recommend biopsy of the solid component of all complex cystic nodules because of the risk of cystic papillary carcinoma. They further suggest that nodules that are “hot on scintigraphy” do not require biopsy.

KSTR Guidelines

In 2011, the KSTR published guidelines for management of thyroid nodules using a different approach. They divided nodules into 3 categories: probably benign, suspicious for malignancy, and indeterminate. Nodules considered probably benign include spongiform nodules and completely cystic or predominantly cystic nodules. Nodules are considered suspicious for malignancy if they have a taller than wide shape, irregular margins, marked hypoechoic echotexture, macrocalcifications or microcalcifications, extracapsular extension, or a spiculated margin. Nodules that cannot be classified in the probably benign or suspicious for malignancy category are considered indeterminate.

The recommendation for biopsy is based on both the category and the size of the nodule. For those nodules considered probably benign, the KSTR guidelines recommend that no follow-up ultrasonography is needed if the nodule is smaller than 1 cm in diameter. For nodules larger than 1 cm and probably benign, they recommend a follow-up ultrasound study at 2 years and at 3 to 5 years. Finally, they recommend “selective use of biopsy” for those nodules thought to be probably benign but larger than 2 cm. The KSTR guidelines recommend biopsy of all nodules exhibiting any feature suspicious for malignancy. They acknowledge, however, that nodules smaller than 5 mm are difficult to biopsy and thus recommend selective fine-needle aspiration biopsy based on the risk factors of the patient and the experience of the clinician. The guidelines recommend biopsy of all nodules larger than 5 mm with a suspicious feature, “if feasible.” The KSTR guidelines also recommend a repeated biopsy of any suspicious nodule with benign initial cytologic findings.

For nodules considered indeterminate, with neither benign nor suspicious features, the KSTR guidelines recommend follow-up ultrasonography if the nodule is smaller than 1 cm and biopsy for all such nodules larger than 1 cm. Finally, they recommend that any nodule showing growth (defined as a 20% increase in diameter or a 50% increase in volume) should undergo biopsy.

Why Does Size of a Nodule Have a Central Role in Guidelines?

All available guidelines use size criteria to select thyroid nodules for biopsy. Numerous studies have shown poor or no correlation between size of thyroid nodules and risk of malignancy. The risk of metastatic involvement (and therefore mortality), however, does have an association with nodule size. The ATA guidelines state that most small malignant lesions are associated with a favorable outcome. They acknowledge that there are rare situations in which subcentimeter microcarcinomas will have locoregional or distant metastatic lesions. They state, however, that, …attempts to diagnose and treat all small thyroid cancers in an effort to prevent these rare outcomes would likely cause more harm than good.

Similarities and Differences

The 3 foregoing sets of guidelines for management of thyroid nodules have numerous similarities and several disparities. With limited prospective studies regarding cost or outcome, many of the recommendations in all 3 sets are based on expert opinion. All recommend biopsy of any thyroid nodule larger than 1 cm in diameter with suspicious features, including microcalcifications, profoundly hypoechoic echotexture, taller than wide shape, or infiltrative margins. The AACE and KSTR guidelines recommend that nodules of any size with suspicious features undergo biopsy, whereas the ATA guidelines do not recommend biopsy of subcentimeter nodules unless the patient has a high-risk history. The KSTR guidelines discuss clinical risk factors in the introduction but, unlike the other guidelines, do not use them in the decision process determining the need for biopsy. The ATA and AACE guidelines consider intranodular vascularity to be a risk factor for malignancy. On the basis of recent data from Moon et al^[4] and others, however, the KSTR guidelines do not consider vascularity as a risk factor.

There are several other discrepancies among the guidelines. For example, a thyroid nodule between 6 and 9 mm with suspicious features (other than microcalcifications) would undergo biopsy on the basis of the AACE and KSTR guidelines but not the ATA guidelines. An isoechoic or hyperechoic nodule larger than 1 to 1.5 cm would undergo biopsy on the basis of the ATA and KSTR guidelines, but the AACE guidelines do not provide guidance regarding isoechoic and hyperechoic nodules. As suggested by Bonavita et al,^[5] hyperechoic nodules in a background of thyroiditis are very likely benign and may not necessitate biopsy.

The 3 sets of guidelines have very different approaches to the management of complex cysts. The ATA guidelines recommend biopsy of all complex cysts larger than 1.5 to 2 cm in diameter. Because of the risk of cystic papillary carcinoma, the AACE guidelines recommend biopsy of all complex cysts. Complex cysts can vary from a predominantly cystic lesion, with a tiny benign-appearing solid mural component, to a predominantly solid lesion with cystic components. The solid components can have benign or suspicious features. The ATA and AACE guidelines do not consider the numerous potential variations in complex cysts. The KSTR guidelines recommend biopsy only if suspicious features are detected in the solid component—a recommendation that makes more sense than use of size criteria alone.

Unfortunately, very few thyroid nodules will escape biopsy under each set of guidelines. Each of the guidelines recommends biopsy for the vast majority of nodules, even those without suspicious features, when they are larger than 1 cm in diameter. In light of the epidemic proportions of thyroid nodular disease, coupled with the overall favorable outcome of most cases of thyroid cancer (many of which likely remain undiagnosed throughout a patient’s life), many patients will undergo biopsy and a surgical procedure for a disease that possibly would not have an adverse outcome if simply followed without intervention.

Which Nodules Can Be Monitored Without Biopsy?

The ATA guidelines do not recommend biopsy for thyroid nodules smaller than 5 mm in diameter, even if suspicious features are present. Solid nodules smaller than 1 cm escape biopsy if no clinical risks or microcalcifications are present. Pure cysts do not require biopsy, nor do spongiform nodules smaller than 2 cm. Biopsy is not recommended for complex cysts smaller than 1.5 to 2 cm (even if suspicious features are present).

The AACE guidelines do not recommend biopsy of solid nodules smaller than 1 cm in diameter if the patient has no clinical risks and there are no suspicious features on ultrasonography. Nodules hyperfunctioning on scintigraphy do not require biopsy.

Similarly, the KSTR guidelines do not recommend biopsy of nodules smaller than 1 cm without suspicious features. In addition, biopsy is considered unnecessary for spongiform nodules and simple cysts smaller than 2 cm in diameter.

Conclusion

The 3 current sets of guidelines provide excellent guidance regarding the management of thyroid nodules. As previously stated, this brief commentary addresses only a minute fraction of the comprehensive knowledge base presented in the complete guidelines.^[1–3] The ATA is currently planning to issue revised guidelines in 2013. They have been actively seeking input regarding areas of agreement and disagreement with the current guidelines. It is my hope that the revised version will add a discussion of the effect of mitigating factors such as age, comorbidities, and life expectancy on the decision to perform a biopsy. Many elderly or chronically ill patients may be better served by careful observation than intervention, and updated guidelines should provide direction in this decision process. Following the lead of the KSTR guidelines, a more comprehensive set of recommendations regarding risk stratification of complex cysts would be welcomed. Similarly, the guidelines should discuss whether more low-risk thyroid nodules can be safely monitored with serial ultrasonography, considering the risk of missing a low-grade thyroid cancer versus the risks associated with a surgical procedure for malignant or benign thyroid disease.

[ CLOSE WINDOW ]

References

1. Cooper DS, Doherty GM, Haugen BT, et al (American Thyroid Association [ATA] Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer). Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–1214.
2. Gharib H, Papini E, Paschke R, et al (AACE/AME/ETA Task Force on Thyroid Nodules). American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 2010;16(suppl 1):1–43.
3. Moon WJ, Baek JH, Jung SL, et al (Korean Society of Thyroid Radiology [KSThR]; Korean Society of Radiology). Ultrasonography and the ultrasound-based management of thyroid nodules: consensus statement and recommendations. Korean J Radiol. 2011;12:1–14.
4. Moon HJ, Kwak JV, Kim MJ, Son EJ, Kim EK. Can vascularity at power Doppler US help predict thyroid malignancy? Radiology. 2010;255:260–269.
5. Bonavita JA, Mayo J, Babb J, et al. Pattern recognition of benign nodules at ultrasound of the thyroid: which nodules can be left alone? AJR Am J Roentgenol. 2009;193:207–213.

Abbreviations
AACE = American Association of Clinical Endocrinologists; AME = Associazione Medici Endocrinologi; ATA = American Thyroid Association; ETA = European Thyroid Association; KSTR = Korean Society of Thyroid Radiology

Endocr Pract. 2012;18(4):596-599. © 2012 American Association of Clinical Endocrinologists