ENDOCRINECONSULT

To Cut or Not to Cut? Evaluating Surgical Criteria for Benign & Nondiagnostic Nodules Ashlyn Smith, MMS, PA-C

new-onset thyroid nod- thyroid surgery, if possible. Her evaluated in the past, and if it has ule, found on exam or in- most recent thyroid US, performed changed significantly. Acidentally on imaging, is a three months ago, showed a right A thorough history can identify common presentation at primary lobe with multiple colloid nodules risk factors for malignancy, which care and specialist clinics. Palpa- with inspissated colloid, the larg- include a personal history of can- ble nodules are present in 4% to est of which is 1.5 cm, and a 4-cm cer or radiation exposure, as well 7% of the population.1 However, complex, solid, cystic nodule with as a family history of thyroid can- more sensitive evaluation with inspissated colloid in the cystic cer or malignant endocrine syn- thyroid ultrasound (US) suggests spaces replacing the entire left dromes. an incidence as high as 70%.2 thyroid lobe. According to the American Felicia denies any family or per- Cancer Society, in 2015, there HISTORY sonal medical history concerning were approximately 62,450 new The first step is establishing a for malignancy. She notes that she cases of thyroid cancer in the history of the nodule(s) in ques- has two sisters with MNG. She de- United States (with 2.5 times as tion. Key questions are listed in nies any neck pain, compressive/ many occurring in women as in Table 1. The onset and progres- obstructive symptoms, and hypo- men).3 In fact, thyroid cancer is sion of a must or hyperthyroid symptoms. the most rapidly increasing cancer be determined; ideally, the pro- in the United States—attributable vider should review any previ- She reports that she was found in part to the increased use of thy- ous studies related to the thyroid to have a goiter on exam and roid US and incidental detection.3 gland. This will help determine if was subsequently diagnosed with The high prevalence of thyroid the nodule is new, if it has been MNG in 2008. Thyroid US showed nodules makes appropriate eval- a 2.3-cm complex, largely solid uation and treatment crucial. This mass in the right mid-pole and a article, through a case study, ex- TABLE 1 3.3-cm largely cystic lesion in the plores the evaluation of a thyroid Key History Questions left mid-pole. She was referred for nodule and the recommendation right-sided fine-needle aspiration for and against thyroidectomy. Is this a new nodule or the first (FNA); results were consistent evaluation of the nodule? with benign colloid nodule. The Felicia, 49, presents to the endo- Was any imaging, serology, left-sided nodule was not biop- crine clinic as a new patient with or histologic evaluation of sied at that time, due to a largely questions about multinodular goi- the thyroid nodule(s) done cystic component. ter (MNG). She has been advised previously? by ENT to have a left-sided domi- Has the nodule changed in size Felicia underwent a follow-up US nant nodule surgically removed or characteristics over time? in 2011; it showed a 1.6-cm right while under anesthesia during her mid-pole nodule with multiple Is there a family history of upcoming chronic sinusitis sur- nonspecific echogenic areas; a thyroid cancer or multiple gery. Felicia would like to avoid endocrine neoplasia type 2? 1-cm benign-appearing nodule; and a 3.7-cm highly vascular het- Is there a personal medical Ashlyn Smith is an endocrinology PA at erogeneous mass with some col- history of cancer or radiation loid components with indetermi- Endocrinology Associates in Scottsdale, exposure? Arizona. nate component in the left lower

34 Clinician Reviews • AUGUST 2016 clinicianreviews.com and mid-pole. She reports that she TABLE 2 did not follow up in 2011. Her next Thyroid Nodule Characteristics evaluation was the current thyroid Concerning for malignancy Likely benign US. She has never had FNA of the Hypoechoic Purely cystic left-sided dominant nodule. Microcalcifications Colloid SYMPTOMATIC VS > 1 cm and solid/hypoechoic < 1 cm without suspicious characteristics ­ASYMPTOMATIC Irregular margins THYROID NODULES Tall > wide Evaluation of a symptomatic thy- Extracapsular growth roid nodule can help to determine Associated cervical the need for surgery, as well as as- lymphadenopathy sess the level of interference with a patient’s activities of daily living and the potential for functional ab- mine the most appropriate course ings or family history—serologic normalities. However, both local of action. screening for abnormal calcito- neck and constitutional symptoms Palpation can be used to nin level may be indicated.4,5 may be nonspecific and unrelated evaluate for a larger and/or fixed to the thyroid gland’s structure or nodule, thyroid gland/nodule Felicia’s lab results include a TSH function. Therefore, the provider tenderness, and cervical lymph- of 1.30 µIU/mL (reference range, should exercise caution in mak- adenopathy. Physical exam can 0.30-3.00 µIU/mL). Based on this ing recommendations based on also assess for signs of hypo- or hy- finding, what (if any) further se- reported symptoms alone. perthyroidism, including abnor- rologic testing is recommended? Symptoms indicative of the mal pulse rate or blood pressure, None: With normal TSH and no need for surgical intervention in- tremor, hypo- or hyperreflexia, concerning family or personal his- clude neck pain, increased neck and integumentary abnormalities tory, additional laboratory evalua- pressure, foreign body sensation, (eg, hair loss, abnormal skin tem- tion is not indicated. dysphonia, dyspnea, and dys- perature, and nail changes). phagia. However, it is essential IMAGING A THYROID NODULE to determine if these symptoms SEROLOGIC EVALUATION Thyroid US is the most sensitive are likely due to a thyroid nod- If a thyroid nodule is suspected imaging study for evaluating thy- ule or if they can be attributed to on exam or found on imaging, roid nodule characteristics. Thy- a secondary cause (eg, postnasal assessment of thyroid function, roid uptake and scan is not indi- drip, vocal cord dysfunction, gas- via thyroid-stimulating hormone cated unless TSH is suppressed troesophageal reflux disease, or (TSH) measurement, is the rec- and evaluation for toxic nodular esophageal stricture). ommended first step. If TSH is goiter is needed. Additional im- If the findings are inconsistent elevated, further evaluation for aging studies, such as CT or MRI, with the clinical picture, second- is recommend- are not recommended for thyroid ary evaluation is prudent to avoid ed, with testing for free thyroxine nodule evaluation. an unnecessary procedure. (T4) and antithyroid peroxidase (TPO) antibodies.4 If TSH is sup- Based on the thyroid US, what PHYSICAL EXAM pressed, further evaluation with characteristics of Felicia’s nodule Palpation of a thyroid nodule is free T4 and assessment for under- are suggestive of a benign nod- an unreliable indicator of risk for lying causes of ule? Of a malignant nodule? (See malignancy. Palpation alone does are indicated, including work-up Table 2.) not allow for detection of all nod- for toxic nodular goiter. ules, particularly smaller ones, Routine monitoring of serum FNA of the left-sided dominant nod- and specific characteristics are calcitonin level is not recom- ule is indicated, based on the US not discernible. Imaging studies mended. However, if there is findings of a partially solid compo- are required to accurately evalu- suspicion for medullary thyroid nent and size > 1 cm. Unfortunately, ate a thyroid nodule and deter- cancer—based on either US find- FNA is nondiagnostic, because it

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yielded cystic fluid only with scant nodules that underwent repeat surgery, an informed decision follicular cells for evaluation. FNA, the risk was 0% for those between provider and patient can that were again nondiagnostic. ultimately be reached. NOW WHAT? This significant difference led the While FNA most definitively distin- author to conclude that “patients Would thyroidectomy be recom- guishes between benign and ma- with two sequential nondiagnos- mended for Felicia? After a thor- lignant nodules, the test is limited. tic thyroid aspirates have a very ough discussion, it is decided that An indeterminate, or nondiagnos- low risk of malignancy.”7 surgery is not indicated at this tic, finding occurs in 10% to 15% of Consider the time commit- time. Relevant factors include the cases and is more likely in nodules ment, financial burden, and benign thyroid US characteristics, with a large cystic component.1 emotional cost for the patient of lack of clinical neck compressive Even a benign finding on FNA repeated evaluation with thyroid symptoms, and patient preference. of a larger nodule should be US and possibly FNA. In recurrent viewed with caution, since aspira- cases, the risks associated with According to the American Thyroid tion is unlikely to pinpoint small surgery begin to be outweighed Association guidelines, Felicia’s insidious malignant cells nestled by the cost and burden of pro- risk for malignancy for the nodule among a larger collection of be- longed observation. in question is < 3%, since it is a nign tissue.3 In many situations, a partially cystic nodule without any patient receives FNA results and Benign nodules suspicious sonographic features. asks, “What should we do now?” With a biopsy-proven benign nod- By foregoing surgery, Felicia will ule, observation is recommended need repeated imaging studies Nondiagnostic nodules unless certain criteria are present: and possibly repeat serologic stud- When FNA is indeterminate, the local neck compressive/obstruc- ies and FNA in the future. CR next step depends on the char- tive symptoms that can be confi- acteristics of the nodule. For a dently attributed to a thyroid nod- REFERENCES solid nodule, repeat FNA is rec- ule; patient preference (eg, due to 1. Stang MT, Carty SE. Recent developments in ommended.4,5 For nodules with anxiety or aesthetics); or higher predicting thyroid malignancy. Curr Opin Oncol. 2008;21(1):11-17. repeatedly nondiagnostic FNAs, index of suspicion (eg, history of 2. Hambleton C, Kandil E. Appropriate and the American Academy of Clini- previous radiation exposure, pro- accurate diagnosis of thyroid nodules: a cal Endocrinologists and the gressive nodule growth, or suspi- review of thyroid fine-needle aspiration. Int J 4,5 Clin Exp Med. 2013;6(6):413-422. American Thyroid Association cious characteristics on US). 3. American Cancer Society. Thyroid cancer recommend that a solid nodule If surgical removal of a benign (2014). www.cancer.org/acs/groups/cid/ be considered for surgical remov- thyroid nodule is recommended, documents/webcontent/003144-pdf.pdf. Accessed June 29, 2016. al unless the nodule has “clearly it is imperative to discuss the risks 4. Gharib H, Papini E, Garber J, et al; AACE/AME/ favorable clinical and US fea- with patients. In addition to tra- ETA Task Force on Thyroid Nodules. American tures.”4,5 ditional surgery risks, thyroidec- Association of Clinical Endocrinologists, Asso- ciazione Medici Endocrinologi, and European Surgical excision should be tomy is associated with transient Thyroid Association medical guidelines for considered for cysts that recur, or permanent postoperative hy- clinical practice for the diagnosis and manage- those that are larger (> 4 cm), and poparathyroidism, as well as vo- ment of thyroid nodules—2016 Update. Endocrine Pract. 2016;22(suppl 1):1-60. those that are repeatedly nondi- cal hoarseness or changes in vo- 5. Haugen BR, Alexander EK, Bible KC, et al; The agnostic on FNA. Personal and cal quality due to the proximity of American Thyroid Association Guidelines family history should be taken the recurrent laryngeal nerve. Ad- Task Force on Thyroid Nodules and Differen- tiated Thyroid Cancer. 2015 American Thy- into account when nodules that ditionally, patients should be ad- roid Association Management Guidelines for are nondiagnostic on FNA dem- vised of the potential for surgical Adult Patients with Thyroid Nodules and Dif- onstrate suspicious characteris- hypothyroidism with hemithy- ferentiated Thyroid Cancer. Thyroid. 2016; 6 26(1):1-133. tics on US. roidectomy and certain irrevers- 6. Yeung MJ, Serpell JW. Management of the An analysis by Renshaw deter- ible hypothyroidism with total solitary thyroid nodule. Oncologist. 2008; mined that risk for malignancy in thyroidectomy. 13(2):105-112. 7. Renshaw A. Significance of repeatedly non- a nodule with a single nondiag- After a discussion of the risks diagnostic thyroid fine-needle aspirations. nostic FNA was about 20%. For and cost of observation versus Am J Clin Pathol. 2011;135(5):750-752.

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