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scanning Small inflammatory nodes may be detected postoperatively and do not necessarily indicate metastatic disease, but follow-up is necessary Ultrasound-guided FNA biopsy should be performed on suspicious lesions 2 Serum thyroglobulin (Tg) Thyroglobulin is produced by normal thyroid tissue and by most differentiated thyroid carcinomas It is only after a total or near-total thyroidectomy and 131I remnant ablation that Tg becomes a useful tumor marker for patients with differentiated papillary or follicular thyroid cancer The usefulness of serum Tg may be negated by the presence of anti-thyroglobulin antibodies Anti-Tg antibodies tend to persist but may become less evident several years after total thyroidectomy and during the last trimester of pregnancy Anti-Tg antibodies mainly interfere with immunometric assays (IMA) used by commercial laboratories Radioimmunoassays are less affected by AgAb interference and may be requested specially For patients without serum anti-Tg antibodies, Tg measurement is a very useful tumor marker Detectable levels of thyroglobulin are commonly encountered in patients who have had incomplete thyroidectomies and 131I remnant ablations Detectable thyroglobulin levels do not necessarily indicate the presence of residual or metastatic thyroid cancer However, baseline or stimulated serum Tg levels 2 ng/mL indicate the need for a repeat neck ultrasound and further scanning If serum Tg levels remain 2 ng/ mL in the presence of normal scanning, it is prudent to repeat the serum Tg in a national reference laboratory Rising serum levels of thyroglobulin are particularly worrisome In one series of patients with differentiated thyroid cancer following thyroidectomy, there was a 21% incidence of metastases in patients with serum Tg < 1 ng/mL (while receiving thyroxine for TSH suppression) Therefore, stimulated serum Tg measurements should be used and always with neck ultrasound The usefulness of routinely doing a radioiodine scan (see below) in low-risk patients is controversial but continues to be done in many centers during stimulation following either rhTSH or thyroid hormone withdrawal, according to the protocols described below 3 Radioactive iodine (RAI: 131I or 123I) whole-body scanning Despite its limitations, RAI has traditionally been used to detect metastatic differentiated thyroid cancer and to determine whether the cancer is amenable to treatment with 131 I RAI scanning is particularly useful for high-risk patients and those with persistent anti-thyroglobulin antibodies that make serum thyroglobulin determinations unreliable The 131I isotope may be used in scanning doses of < 3 mCi (111 MBq) or given within 2 weeks of RAI treatment to avoid stunning metastases such that they take up less of the RAI therapy dose The radioisotope 123I may be used in scanning doses of 5 mCi (185 MBq), does not stun tumors, and allows single-photon emission computed tomography (SPECT) to better localize metastases Initial RAI scanning is typically performed about 2 4 months following surgery for differentiated thyroid carcinoma Whole-body scanning should be performed for at least 30 minutes for at least 140,000 counts and spot views of the neck should be obtained for at least 35,000 counts.

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About 65% of metastases are detectable by RAI scanning, but only after optimal preparation: Patients should ideally have a total or near-total thyroidectomy, since any residual normal thyroid competes for RAI with metastases, which are less avid for iodine To avoid nonradioactive iodine competitive inhibition of RAI uptake, intravenous iodinated contrast must be avoided for at least 2 months before scanning; patients must follow a low-iodine diet for at least 2 weeks before scanning and continue to limit iodine consumption until the scan is complete or until after 131I therapy In addition, patients must have high levels of TSH to stimulate metastases to take up more RAI, making them visible on scanning This can be accomplished by allowing the patient to become hypothyroid or by administering synthetic rhTSH The use of rhTSH has become more widespread for surveillance scanning and stimulated thyroglobulin determinations following thyroidectomy for differentiated thyroid carcinoma, due to its convenience for the patient However, rhTSH-stimulated scanning is slightly less sensitive than hypothyroid-stimulated scanning For stage I II patients, it is reasonable to perform a thyroid-withdrawal scan once; if it is negative and the serum thyroglobulin is < 2 ng/mL, an rhTSH scan can be performed 1 and 3 years thereafter a Thyrotropin-stimulated serum Tg and radioiodine scanning The use of recombinant human thyrotropin- (Thyrogen; rhTSH) injections can replace thyroid withdrawal with much less discomfort for most patients Thyrotropin stimulates uptake of RAI and production of thyroglobulin by differentiated thyroid cancer or residual thyroid The use of rhTSH is particularly suited to low-risk patients: those with a small papillary thyroid carcinoma who have had a total or near-total thyroidectomy and have no known local or distal metastases and a serum thyroglobulin < 1 mcg/L during thyroxine suppression of serum TSH In about 21% of such low-risk patients, rhTSH stimulates serum thyroglobulin to above 2 mcg/L; such patients have a 23% risk of local neck metastases and a 13% risk of distant metastases Stimulated radioiodine neck and whole-body scanning can detect only about half of these metastases because they are small or not avid for iodine Thyrotropin must be kept refrigerated and may be administered according to the following protocol: Thyroxine replacement is held for 2 days before rhTSH and for 3 days afterward On Monday and Tuesday, thyrotropin 09 mg is administered intragluteally (not intravenously) On Wednesday, serum is drawn for TSH and thyroglobulin determinations Immediately thereafter, RAI is administered in a scanning dose (see above) On Friday, serum is drawn for thyroglobulin and the whole-body scan is performed Side effects of thyrotropin injections include nausea (11%) and headache (7%) Hyperthyroidism can occur in patients with significant metastases or residual normal thyroid Thyrotropin has caused neurologic deterioration in 7% of patients with central nervous system metastases The combination of thyrotropin-stimulated scanning and thyroglobulin levels detects a thyroid remnant or cancer with a sensitivity of 84% However, the presence of anti-thyroglobulin antibodies renders the serum thyroglobulin determination uninterpretable Thyrotropin stimulation does not.

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