WORKUP	Section 5 of 11
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Lab Studies:

• Thyroid function: Perform complete assessment of thyroid function in any patient with thyroid lumps. Available studies are not specific for FTC.

• Levels above the reference range of thyroxine (T4; reference range, 4.5-12.5 mcg/dL), triiodothyronine (T3; reference range, 100-200 ng/dL), and TSH (reference range, 0.2-4.7 mIU/dL) may indicate thyroid cancer.

• Evaluate serum levels of thyroglobulin, calcium, and calcitonin.

• Determining serum level of carcinoembryonic antigen (CEA) may be helpful; the reference value is less than 3 ng/dL. However, the implications of CEA elevation are not specific because CEA levels elevate in several cancers, and many healthy people may have small amounts of CEA, especially pregnant women and heavy smokers.

• TSH suppression test: Cancer is autonomous and does not require TSH for growth, whereas benign lesions do. Therefore, when exogenous thyroid hormone feeds back to the pituitary to decrease the production of TSH, thyroid nodules that continue to enlarge are likely to be malignant. However, consider that 15-20% of malignant nodules are suppressible.

• Preoperatively, the test is useful for patients with nontoxic solitary benign nodules and for women with repeated inconclusive test results.

• Postoperatively, the test also is useful in follow-up of FTC cases.

Imaging Studies:

• Chest radiography, CT scanning, and MRI usually are not used in the initial workup of a thyroid nodule, except in patients with clear metastatic disease at presentation. These tests are second-level diagnostic tools and are useful in preoperative patient assessment.

• Echography is the first imaging study that must be performed in any patient with suspected thyroid malignancy.

• Echography is noninvasive and inexpensive, and it represents the most sensitive procedure for identifying thyroid lesions and determining the diameter of a nodule (2-3 mm).

• Echography also is useful to localize lesions when a nodule is difficult to palpate or is located deeply.

• Echography can determine whether a lesion is solid or cystic and can detect the presence of calcifications.

• The rate of accuracy of echography in categorizing nodules as solid, cystic, or mixed is near 90%.

• Ultrasonography may direct a fine-needle aspiration biopsy (FNAB).

• Thyroid echography has some disadvantages: it cannot be used to distinguish benign nodules from malignant nodules, and it cannot be used to identify true cystic lesions.

• Pulsed and power Doppler echography may provide important information about the vascular pattern and the velocimetric parameters. Such information can be useful preoperatively to reach a correct differential diagnosis of malignant or benign thyroid lesion.

• Prior to FNAB, thyroid scintigraphy (or thyroid scanning) performed with technetium Tc 99m pertechnetate (99mTc) or radioactive iodine (I-131 or I-123) was the initial diagnostic procedure of choice in thyroid evaluation.

• The procedure is not as sensitive or specific as FNAB in distinguishing benign nodules from malignant nodules.

• The scintigraphy procedure performed with 99mTc has a high error rate because 99mTc is trapped as is iodide but is not organified in the thyroid. 99mTc has a short half-life and cannot be used to determine functionality of a thyroid nodule.

• Radioactive iodine is trapped and organified in the thyroid and can be used to determine functionality of a thyroid nodule. Iodine-containing compounds and seafood interfere with any tests that use radioactive iodine. Scintigraphic images of the thyroid are acquired 20-40 minutes after IV administration of radionuclide. In more than 90% of cases, clearly benign nodules appear as hot nodules because they are hyperfunctioning and have a high captation rate of radionuclide and, physiologically, of iodine. Malignant nodules usually appear as cold nodules because they are not functioning.

• Thyroid scanning is helpful and specific in localizing the tumor preoperatively and residual thyroid tissue immediately postoperatively. It also is used to follow-up for tumor recurrence or metastasis. Thyroid scanning could be useful in diagnosing thyroid tumors in patients with benign lesions (by FNAB) or solid lesions (by echography).

Other Tests:

• Perform indirect or fiberoptic laryngoscopy to evaluate airway and vocal cord mobility and to have preoperative documentation of any unrelated abnormalities.

Procedures:

• FNAB actually is considered the best first-line diagnostic procedure for a thyroid nodule; it is a safe and minimally invasive test.

• Local anesthesia is administered at the puncture site, and the aspiration biopsy needle is guided into the mass. The nodule is held with the fingers of the left hand while a needle is introduced through the skin into the nodule with the right hand.

• After aspiration with a 21G or 23G needle, the material is disposed on a glass slide, fixed with alcohol-acetone, and stained according to the technique of Papanicolaou.

• Accuracy of FNAB is better than any other test for uninodular lesions. Sensitivity of the procedure is near 80%, specificity is near 100%, and errors can be diminished using ultrasound guidance. False-negative and false-positive results occur less than 6% of the time.

• A cytologist could experience difficulty in distinguishing some benign cellular adenomas from their malignant counterparts (ie, follicular and Hürthle cell adenomas from carcinomas).

• Thyroid biopsy could be performed using the classic Tru-Cut or Vim-Silverman needles, but FNAB is preferable. Patients comply best with FNAB.

	TREATMENT	Section 6 of 11
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Medical Care:

• About 4-6 weeks after surgical thyroid removal, patients must have radioiodine to detect and destroy any metastasis and any residual tissue in the thyroid. Administer therapy until no further radioiodine uptake is noted.

• Patients will take thyroid replacement therapy (ie, L-thyroxine [L-T4]) for life, especially after total thyroidectomy. This entails taking 2.5-3.5 mcg/kg of L-T4 every day.

• A number of indications for external beam radiation (RT) apply to the management of FTC.

• If all gross disease cannot be resected, or if residual disease is not avid for radioactive iodine, external beam RT often is employed for locally advanced disease.

• Similarly, RT is indicated for unresectable disease extending into adjacent structures, such as the trachea, esophagus, great vessels, mediastinum, and/or connective tissue. In this situation, RT doses of 6000-6500 cGy typically are used.

• Following RT for unresectable disease, the patient should undergo I-131 scanning. If uptake is detected, a dose of I-131 should be administered.

• External beam RT also may be used after resection of recurrent FTC that is no longer avid for radioactive iodine.

• In the postoperative setting, RT doses of 5000-6000 cGy commonly are delivered to the tumor bed to reduce the risk of local-regional recurrence.

• Careful treatment planning (typically with multiple RT fields) should be employed to minimize the risks of RT complications.

• Finally, a palliative course of RT is useful to relieve pain from bone metastases.

• Chemotherapy with cisplatin or doxorubicin has limited efficacy, producing occasional objective responses (generally for short durations). Because of the high toxicity of chemotherapy with cisplatin or doxorubicin, it may be considered in symptomatic patients with recurrent or advancing disease. It could improve quality of life in patients with bone metastases, but no standard protocol exists for chemotherapy of metastatic FTC.

Surgical Care: Surgery is the definitive management of thyroid cancer, and various types of operations may be performed.

• Lobectomy with isthmectomy

• This represents the minimal operation for a potentially malignant thyroid nodule.

• Patients younger than 40 years who have FTC nodules that are less than 1 cm in size, well defined, minimally invasive, and isolated may be treated with hemithyroidectomy and isthmectomy.

• Subtotal thyroidectomy (near total thyroidectomy)

• Subtotal thyroidectomy is preferable if it is feasible, since it carries a lower incidence of complications (eg, hypoparathyroidism, superior and/or recurrent laryngeal nerve injury).

• Moreover, total thyroidectomy does not improve the long-term prognosis.

• Total thyroidectomy (removal of all thyroid tissue preserving the contralateral parathyroid glands)

• Approximately 10% of patients who have had total thyroidectomy demonstrate cancer in the contralateral lobe. Therefore, residual thyroid tissue has the potential to dedifferentiate to anaplastic cancer.

• Perform total thyroidectomy in patients who are older than 40 years with FTC and in any patient with bilateral disease; furthermore, recommend total thyroidectomy to anyone with a thyroid nodule and a history of irradiation.
  • Some studies show lower recurrence rates and increased survival rates in patients who have undergone total thyroidectomy.

  • This surgical procedure also facilitates earlier detection and treatment of recurrent or metastatic carcinoma.

  • This surgical option is mandatory in patients with FTC ascertained by postoperative histologic studies (ie, if a very well-differentiated tumor is discovered) after a one-side lobectomy, with or without isthmectomy.

• When the primary tumor has spread outside the thyroid and involves adjacent vital organs, eg, larynx, trachea, or esophagus, preserve these organs at the first surgical approach. However, the surrounding soft tissues, including muscles and involved areas of the trachea and/or esophagus, may be sacrificed whenever they are involved directly in the differentiated thyroid carcinoma and their local resection is easily feasible.

Consultations:

• Schedule elderly patients for cardiologic assessment because of the high risk of subclinical hypothyroidism episodes.

• Consult an otolaryngologist, especially in patients with thyroid disease who have voice disturbances.

	MEDICATION	Section 7 of 11
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The most useful drugs for postsurgical treatment of FTC are L-thyroxine (L-T4) and radioiodine. For metastases, antineoplastic drugs, eg, cisplatin and doxorubicin, may be useful for palliation.

	MISCELLANEOUS	Section 9 of 11
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Medical/Legal Pitfalls:

• The main medical and legal problems related to FTC concern vocal cord paralysis due to damage of the recurrent laryngeal nerve, damage of the parathyroid glands that leads to temporary or permanent hypoparathyroidism, and toxic side effects of radioiodine administration. For this reason, always obtain an informed consent to diagnostic procedures and treatment that explains all the procedures and their possible complications.

Special Concerns:

• Because radioiodine treatment may cause either teratogenesis or spontaneous abortions, patients should delay pregnancy for at least one year after radioiodine treatment.