Approach
Approach to Recurrent Differentiated Thyroid Cancer
During the postoperative period, the clinician should be aware of the signs of residual or recurrent thyroid cancer. Persistently elevated thyroglobulin after surgery and/or focal radioiodine avidity suggests residual tumor burden or residual functioning thyroid tissue. When thyroglobulin is elevated due to tumor burden, it may be due to residual primary tumor, locoregional disease, nodal, or distant metastases. Suspicious lesions found on physical examination, radiologic examination, or radioiodine scan should have a biopsy performed on them by ultrasound-guided fine-needle aspiration (FNA). Alternative strategies must be used for surveillance and treatment when radioiodine avidity is lost or when thyroglobulin is not a valid tumor marker.
After thyroidectomy and radioiodine remnant ablation, several methods are used to follow patients with differentiated thyroid cancer, including serum thyroglobulin levels, ultrasonography of the neck, iodine-131 (131 I) whole body scintigraphy (WBS), and scintigraphy with nonspecific tracers such as technetium-99 m (99m Tc) tetrofosmin, or sestamibi.
Laboratory Studies
Serum thyroglobulin levels
Serum thyroglobulin (Tg) level measurement is the most-used method of early detection and monitoring for recurrent thyroid cancer. Serum Tg levels principally integrate the following 3 variables:
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The mass of thyroid tissue present (benign or neoplastic)
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The degree of thyrotropin (TSH) receptor stimulation
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The tumor's intrinsic ability to synthesize and secrete Tg
Serum Tg levels are part of the preoperative evaluation. When TSH is low (on levothyroxine [LT4] therapy), basal serum Tg may be undetectable and recombinant human thyrotropin (rhTSH) administration may be needed to increase serum Tg into the measurable range. The Tg fold response to rhTSH is an index of the tumor's sensitivity to TSH and is calculated by dividing the rhTSH-stimulated Tg level by the basal Tg level. Normal thyroid remnant and differentiated thyroid cancer (DTC) display a greater (>10-fold) serum Tg response to TSH stimulation compared with less well-differentiated tumors (< 3-fold).
Imaging Studies
Ultrasonography
Ultrasonography is important in the preoperative assessment of patients with thyroid cancer. This technique allows for the detection of cervical lymph node and soft tissue metastasis that is not evident on physical examination. [8] Lesions as small as 4 mm have been reported to be detectable via ultrasonography. This becomes especially helpful in reoperative planning and determination of the need for further neck dissection. Ultrasonography has been shown to be a sensitive technique that can be used to monitor patients for recurrent thyroid carcinoma in the thyroid bed after total thyroidectomy. One potential diagnostic pitfall is the misdiagnosis of normal residual thyroid or parathyroid gland tissue as recurrent tumor. [9] Preoperative high-resolution ultrasound mapping improves the detection and assessment of lymph node metastasis in those patients with persistent or recurrent papillary thyroid cancer (PTC). [10, 11] The authors find preoperative high-resolution neck ultrasoundmappingandmarkinghelpful when it is used prior to reoperative thyroid cases.
Positron emission tomography with 2-(F-18)-fluoro-2-deoxy-D-glucose/CT scanning
Positron emission tomography with 2-(F-18)-fluoro-2-deoxy-D-glucose/CT scanning (PET-FDG/CT) can provide precise anatomic localization of recurrent or metastatic thyroid carcinoma (which leads to improved diagnostic accuracy) and can guide therapeutic management. Two thirds of recurrences or metastases of differentiated thyroid cancer store iodine. [12, 13] Most metastases that are131 I negative demonstrate FDG uptake, which represents rapid tumor growth and poor differentiation, whereas most of the131 I–positive metastases are PET-FDG negative. [12] The sensitivity for detecting131 I-negative metastases with PET-FDG can be increased by elevated thyroid-stimulating hormone (TSH) after withdrawal of thyroid hormone therapy or after intramuscular injection of recombinant TSH.
Iodine-131 whole-body scintigraphy
131 I is the radionucleotide with the highest specificity for DTC. However, only about two thirds of metastases from DTC accumulate iodine. [14] Therefore, in addition to131 I whole-body scintigraphy (WBS), other nonspecific tracers (eg,99m Tc tetrofosmin WBS,99m Tc sestamibi WBS, or PET-FDG) are needed to detect iodine-negative recurrences or metastases. [14]
The combination of131 I-WBS and FDG-PET increases the detection rate to more than 90-95% of cases.
Other imaging modalities
When determining the extent of metastasis in recurrent disease, CT scans and MRI may be valuable in delineating the location and extent of tissue invasion.
Other Tests
Fine-needle aspiration
The sensitivity of ultrasound-guided fine-needle aspiration (FNA) for diagnosing recurrent carcinoma in the thyroid bed after total thyroidectomy was 100% with a specificity of 85.7%. [9]
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Axial CT scan of a patient with a thyroid lesion prior to thyroidectomy.
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Axial CT scan of a patient one year after total thyroidectomy. The great vessels of the neck are significantly medialized.
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Central compartment dissections in the previously operated neck. The recurrent laryngeal nerve (arrow) was traced out from the scarred tracheoesophageal groove.
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Revision neck dissection. Structures encountered that resemble a parathyroid should undergo frozen section biopsy. Exposed tissue adjacent to the great vessels was found to be metastatic papillary thyroid cancer.
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Thyroid gland, anterior and lateral views.
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Distribution of thyroid arteries with associated laryngeal nerve, anterior view.
