When evaluating a patient presenting with thyroid disease, one should inquire about symptoms of hyperthyroidism or hypothyroidism, risk factors for thyroid cancer, and symptoms due to enlargement of the gland. Symptoms of hyperthyroidism include heat intolerance, weight loss, palpitations, hair loss, and diarrhea. Symptoms of hypothyroid include cold intolerance, fatigue, weight gain, constipation, and hoarseness. Thyroid nodules occur in 4% to 7% of the general population. The vast majority of these nodules (95%) are benign. Risk factors for thyroid cancer include hypothyroidism, a family history of thyroid cancer (especially papillary or medullary thyroid cancer), and a history of head/neck irradiation. Large thyroid nodules or diffusely enlarged glands can cause compressive symptoms involving the esophagus, trachea, and recurrent laryngeal nerve such as dyspnea, stridor, orthopnea, dysphagia, or hoarseness. Recent data suggest that even moderately enlarged thyroid gland/nodules can cause significant swallowing dysfunction that is relieved with thyroidectomy.

Signs of hyperthyroidism include elevated pulse, tremor, warm skin, and prominent eyes. Signs of hypothyroidism include dry skin, nonpitting edema, and coarse hair. The thyroid gland can be palpated easily by standing behind the patient and locating the cricoid cartilage. The isthmus lies just below the cricoid. Asking the patient to drink water while palpating the neck with both hands will facilitate localization of thyroid mass since the thyroid moves up and down with swallowing. Thyroid nodules are usually quite firm. It is important to also examine the central and lateral neck lymph nodes for lymphadenopathy.

FNA is a relatively simple and safe procedure, and it is usually performed in the outpatient clinic. The patient is placed in a
supine position with a pillow or towel roll placed behind the shoulder to extend the neck and to bring the thyroid closer to the surface of the skin (Fig. 1). At our institution, the patient often has EMLA cream applied to the skin 20 to 30 minutes prior to the procedure. The skin is then prepped with alcohol, and 1% lidocaine without epinephrine can be injected into the skin for additional local anesthesia. The thyroid mass is localized with ultrasound and immobilized between the fingertips of the nondominant hand. Using the dominant hand, a 23- or 25-gauge 1.5-in. needle with an attached 10-mL syringe is advanced into the lesion, with the clinician noting the consistency of the nodule upon entering. We prefer the nonsuction technique because it results in less trauma and bleeding. If utilizing the suction technique, the syringe is pulled back with the thumb once the lesion has been entered. A syringe-holder aspiration device can facilitate this technique. Once the needle enters the lesion, it is rapidly moved back and forth along a single track for each aspiration until material is seen with the hub of the needle. Suction (if utilized) is released before removal of the needle from the nodule. Firm pressure is applied to the puncture site. Three to six passes are often required to obtain an adequate sample. If a cyst is encountered, the fluid is completely aspirated and sent for cytologic examination. The region of the cyst is then evaluated by ultrasound and any residual solid component reaspirated.

The needle is then detached from the syringe, and the syringe filled with air, reattached, and the contents expelled onto a glass slide. A second slide is placed on top of the first slide and the material is smeared by pulling the slides in opposing horizontal directions. Slides can be either immediately placed into alcohol or sprayed with fixative for Papanicolaou’s stain or air-dried for Diff-Quik (May-Grunwald-Giemsa) staining. The definition of specimen adequacy varies from institution to institution. Usually at least 6 to 10 clusters of cells on two separate slides are required to make a diagnosis. On-site evaluation by a cytopathologist can significantly reduce the inadequacy rate. Complications from FNA are extremely rare but include bleeding/hematoma (<0.5%), tracheal puncture (rare), nodule infarction (<5%), and tumor seeding (<0.005%).

FNAs are usually classified into four categories:

FNAs in the latter category should be repeated as up to 80% may be diagnostic on the repeat attempt.

Papillary thyroid cancer. For lesions <1 cm, either thyroid lobectomy or total thyroidectomy is acceptable. For lesions 1 cm or greater, total thyroidectomy is recommended. If abnormal lymph nodes are seen intraoperatively or by ultrasound, level 6 central lymph node dissection is indicated. In patients with enlarged lateral lymph nodes, FNA should be performed on the lymph node and if positive a compartmentalized lymph node dissection often involving levels 2, 3, and 4 lymph nodes should be done.

Medullary thyroid cancer. Total thyroidectomy with bilateral central (level 6) lymph node dissection is the minimal operation. For patients with abnormal lateral lymph nodes by ultrasound or computed tomography (CT), or in patients with calcitonin levels >1000 pg/mL, modified radical neck dissection should be performed. Because of the association of medullary thyroid cancer with multiple endocrine neoplasia type 2 A (MEN 2 A), preoperative evaluation should include plasma and/or 24 urinary metanephrines for pheochromocytoma, CT scans of the neck, chest, and abdomen for staging, calcium and parathyroid hormone testing for hyperparathyroidism, and RET proto-oncogene testing to assess for familial disease.

Thyroid lymphoma and anaplastic thyroid cancer. These types of thyroid malignancies are primarily treated with chemotherapy and/or radiation therapy. Occasionally, thyroidectomy is performed for early anaplastic cancers, and for palliation of airway compromise from thyroid lymphoma.

Follicular neoplasm. Approximately 80% of follicular neoplasms or lesions are adenoma while 20% are cancer. The presence of capsular and/or vascular invasion on permanent histology distinguishes adenomas from follicular cancers. We generally perform a diagnostic thyroid lobectomy in patients without frozen section. We and others have demonstrated that intraoperative frozen section is misleading and does not provide any additional information >90% of the time. Thus, we wait for permanent histology and if positive for cancer perform a completion thyroidectomy usually within 5 days or after 2 to 3 months from the original thyroid lobectomy. For patients with a follicular neoplasm, we would consider an initial total thyroidectomy for the following: contralateral nodular disease or Hashimoto’s thyroiditis, the patient is already taking thyroid hormone, or patient preference.

Hurthle cell neoplasm. Approximately 70% of Hurthle cell neoplasms or lesions are adenoma while 30% are cancer. Similar to follicular neoplasms, the presence of capsular and/or vascular invasion on permanent histology distinguishes Hurthle cell adenomas from cancers. Likewise, we generally perform a diagnostic thyroid lobectomy in patients without frozen section. If the permanent histology is positive for cancer, we perform a completion thyroidectomy. Many studies have shown that the rate of malignancy for Hurthle cell neoplasms is directly related to the size of the lesion. While cancer is very uncommon with Hurthle cell neoplasms less than 2 cm in size, the rate of cancer exceeds 50% in lesions of a greater size than 4 cm. Thus, we typically recommend a total thyroidectomy for Hurthle cell neoplasms larger than 4 cm. We would also consider a total thyroidectomy in patients with contralateral nodular disease and Hashimoto’s thyroiditis, if the patient was already taking thyroid hormone, or patient preference.

Suspicious, but not diagnostic, of papillary thyroid cancer. An aspirate “suspicious for papillary thyroid cancer” is not the same as an aspirate “diagnostic for papillary thyroid cancer” in regard to likelihood of malignancy and surgical management. The cytologic criteria for papillary thyroid cancer include large monolayer sheets of follicular epithelial cells, enlarged nuclei with powdery chromatin, intranuclear cytoplasmic inclusions and grooves, and papillary structures with or without tall columnar cells. While FNAs diagnostic of papillary thyroid cancer have all of these features, those FNAs that have some but not all of the features of papillary thyroid cancer are read as “suspicious for papillary thyroid cancer.” Multiple reports have shown that FNAs suspicious for papillary thyroid cancer are malignant 50% to 60% of the time. Thus, for a thyroid nodule that is suspicious for papillary thyroid cancer, we would recommend a thyroid lobectomy to
resect the nodule, with intraoperative frozen section analysis. We and others have demonstrated that frozen section is extremely useful with an FNA suspicious for papillary thyroid cancer, as it is accurate 90% of the time. If the frozen section is positive for papillary thyroid cancer, we would perform a total thyroidectomy at that time. If the frozen section is negative, we would terminate the operation having performed only a lobectomy and wait for final histologic evaluation.

The management of a thyroid nodule that is “benign” on FNA is dependent upon the size of the nodule and if the patient has symptoms due to the nodule. Benign nodules generally do not require surgery unless they are causing compressive symptoms (airway compromise, dysphagia, etc.). Data from multiple investigators have shown that thyroidectomy in symptomatic patients can greatly improve quality of life. Thyroidectomy should also be considered in patients with thyroid nodules and a history of head and neck irradiation because of the increased risk of developing thyroid cancer. We generally advocate a total thyroidectomy in patients with thyroid nodules and a history of head and neck irradiation, irrespective of biopsy findings.

Nodule greater or equal to 4 cm in size. While FNA is extremely accurate in delineating most benign from malignant thyroid nodules, several studies have shown that FNA is less reliable with thyroid nodules ≥4 cm. McCoy and colleagues noted that preoperative FNA results in patients with thyroid nodules ≥4 cm were read incorrectly as benign in 13% of patients with cancer; when multifocal micropapillary carcinoma was included, this false-negative rate for preoperative FNA reached 16%. In a study from our group, FNA results reported as benign turned out to be either neoplastic (22/52) or malignant (4/52) on final pathology. Among patients with nondiagnostic FNAs, the risk of malignancy was 27%. We concluded that in patients with thyroid nodules ≥4 cm, FNA results are highly inaccurate, misclassifying half of all patients with reportedly benign lesions on FNA. Furthermore, those patients with a nondiagnostic FNA display a very high risk of differentiated thyroid carcinoma. Therefore, we recommend that diagnostic lobectomy, at a minimum, be performed in patients with thyroid nodules ≥4 cm regardless of FNA cytology. In patients who are asymptomatic and have nodules <4 cm, management usually consists of clinical follow-up with a repeat thyroid ultrasound in 6 months. If the nodule increases in size or becomes worrisome in ultrasound appearance during follow-up, repeat FNA is warranted. Our practice has been to follow small, asymptomatic thyroid nodules at 6, 18, and 42 months.

Hyperthyroidism. Kocher developed subtotal thyroidectomy as the treatment for hyperthyroidism from Graves’ disease, which then became the routine form of therapy for the disease. After the advent of radioactive iodine therapy in the 1930s, surgery became less commonly performed as the primary treatment. There are still a number of important indications for surgical treatment of hyperthyroidism such as age, sex, pregnancy, and lactation, the presence of a thyroid nodule or large goiter (Plummer’s), and patient preference. These factors may guide clinicians to offer surgery as a first-line treatment. For patients with Graves’ disease or Plummer’s disease, total thyroidectomy is the operation of choice and has largely replaced subtotal thyroidectomy, which is associated with a much high recurrence rate and similar morbidity. For patients with hyperthyroidism due to a single hot nodule, unilateral thyroid lobectomy is the best operation.