Table 26–5 illustrates the approach to the evaluation of thyroid nodules based on the index of suspicion for malignancy.
Table 26–5.Clinical evaluation of thyroid nodules.1 ||Download (.pdf) Table 26–5. Clinical evaluation of thyroid nodules.1
|Clinical Evidence ||Low Index of Suspicion ||High Index of Suspicion |
|History ||Family history of goiter; residence in area of endemic goiter ||Previous therapeutic radiation of head, neck, or chest; hoarseness |
|Physical characteristics ||Older women; soft nodule; multinodular goiter ||Young adults, men; solitary, firm nodule; vocal cord paralysis; enlarged lymph nodes; distant metastatic lesions |
|Serum factors ||High titer of thyroid peroxidase antibody; hypothyroidism; hyperthyroidism ||Elevated serum calcitonin |
|Fine-needle aspiration biopsy ||Colloid nodule or adenoma ||Papillary carcinoma, follicular lesion, medullary or anaplastic carcinoma |
|Scanning techniques || || |
| Uptake of 123I ||Hot nodule ||Cold nodule |
| Ultrasonogram ||Cystic lesion ||Solid lesion |
| Radiograph ||Shell-like calcification ||Punctate calcification |
|Response to levothyroxine therapy ||Regression after 0.05–0.1 mg/day for 6 months or more ||Increase in size |
Most small thyroid nodules cause no symptoms. They may sometimes be detected only by having the patient swallow during careful inspection and palpation of the thyroid.
A thyroid nodule or multinodular goiter can grow to become visible and of concern to the patient. Particularly large nodular goiters can become a cosmetic embarrassment. Nodules can grow large enough to cause discomfort, hoarseness, or dysphagia. Nodules that cause ipsilateral recurrent laryngeal nerve palsy are more likely to be malignant. Retrosternal large multinodular goiters can cause dyspnea due to tracheal compression. Large substernal goiters may cause superior vena cava syndrome, manifested by facial erythema and jugular vein distention that progress to cyanosis and facial edema when both arms are kept raised over the head (Pemberton sign).
Depending on their cause, goiters and thyroid nodules may be associated with hypothyroidism (autoimmune thyroiditis, endemic goiter) or hyperthyroidism (Graves disease, toxic nodular goiter, subacute thyroiditis, and thyroid cancer with metastases).
A serum TSH and FT4 determine if the thyroid is hyperfunctioning. Patients with a subnormal serum TSH must have a radionuclide (123I or 99mTc pertechnetate) thyroid scan to examine whether the nodule is hyperfunctioning; hyperfunctioning nodules are usually benign but not reliably so. Very high levels of TPO Ab and Tg Ab are found in autoimmune thyroiditis. However, thyroiditis frequently coexists with malignancy, so suspicious nodules should always be biopsied. Serum calcitonin is obtained if a medullary thyroid carcinoma is suspected in a patient with a family history of medullary thyroid carcinoma or MEN types 2 or 3.
Neck ultrasonography should be performed (see Fine-Needle Aspiration of Thyroid Nodules, below). Malignant nodules are more likely to grow more than 2 mm/year. Ultrasonography is preferred over CT and MRI. CT scanning is helpful for larger thyroid nodules and multinodular goiter; it can determine the degree of tracheal compression and the degree of extension into the mediastinum.
RAI (123I or 131I) scans are not helpful for assessing whether a thyroid nodule is benign or malignant. Hyperfunctioning (hot) nodules are ordinarily benign (but may rarely be malignant). RAI uptake and scanning is helpful mainly for assessing the etiology of hyperthyroidism (eg, hyperfunctioning nodule). (See Hyperthyroidism.)
D. Incidentally Discovered Thyroid Nodules
Thyroid nodules are frequently discovered as an incidental finding, with an incidence that depends on the imaging modality: Ultrasound, about 30% (20% are larger than 1 cm); MRI, 50%; CT, 13%; and 18FDG-PET, 2%. When MRI, CT, and 18FDG-PET detect a thyroid nodule, an ultrasound is performed to better determine the nodule’s risk for malignancy and the need for FNA cytology, and to establish a baseline for ultrasound follow-up. The malignancy risk is about 13–17% for nodules discovered incidentally on CT, MRI, or ultrasound and 25–50% for nodules discovered incidentally by 18FDG-PET. However, most such malignancies are very low grade. For incidentally discovered thyroid nodules of borderline concern, follow-up thyroid ultrasound in 3–6 months may be helpful; growing lesions should be assessed with FNA cytology or resected.
E. Fine-Needle Aspiration of Thyroid Nodules
FNA is the best method to assess a thyroid nodule for malignancy. FNA can be done while patients continue taking anticoagulants or aspirin. For multinodular goiters, the four largest nodules (1 cm or larger) are usually biopsied to minimize the risk of missing a malignancy.
Thyroid nodules are classified for malignancy risk according to their appearance on ultrasound. High-risk nodules (80% malignancy risk) have microcalcifications, irregular margins, extrathyroidal extension, extrusion of soft tissue into a calcified rim, or are taller than wide; such nodules require FNA if they are 1 cm or larger. Intermediate-risk nodules (15% malignancy risk) are hypoechoic and solid; they also usually require FNA if they are 1 cm or larger. Low-risk nodules (7% malignancy risk) are partially cystic with eccentric solid areas; they require biopsy if they are 1.5 cm or larger. Very low-risk nodules (below 3% malignancy risk) are those that are spongiform or simple cysts; FNA is optional if they are 2 cm or larger. Using ultrasound guidance for FNA biopsy improves the diagnostic accuracy for both palpable and nonpalpable thyroid nodules. FNA cytology is typically reported using The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), which divides results into six categories:
Nondiagnostic or unsatisfactory: The malignancy risk is 1–4%. The usual management is a repeat FNA under ultrasound guidance.
Benign: The malignancy risk is about 2.5%. The usual management is clinical follow-up with palpation or ultrasound at 6- to 18-month intervals.
Atypia of undetermined significance (AUS): The malignancy risk is about 14%, higher with sonographic features of malignancy. The usual management is clinical correlation and a repeat FNA.
Suspicious for follicular neoplasm (SFN) or follicular neoplasm (FN): The malignancy risk is about 25%, higher when Hürthle cells are present and in patients over age 50. The usual management is thyroid lobectomy.
Suspicious for malignancy (SFM): The malignancy risk is about 70%. The usual management is thyroid lobectomy or near-total thyroidectomy.
Malignant: The malignancy risk is about 99%. The usual management is a near-total thyroidectomy.
For FNA samples with TBSRTC classified as suspicious categories (4) FN or (5) SFM, a gene-expression classifier has been developed that examines messenger RNA in an effort to more accurately determine the risk of malignancy in a given nodule. However, a Mayo Clinic study reported disappointing results: only 13% of nodules that were suspicious on gene-expression classifier were malignant.
A molecular genetic approach for FNA suspicious nodules assesses the FNA sample for genetic abnormalities associated with thyroid cancer. A BRAF mutation indicates the presence of a papillary thyroid carcinoma with about 98% probability. However, genetic testing for DNA mutations or messenger RNA has not proven sufficiently useful or accurate for suspicious nodules to warrant widespread use.