The Problem of the Patient with Thyroglobulin Elevation but Negative Iodine Scintigraphy: The TENIS Syndrome
Section snippets
TSH Suppression
What then are the available for the treatment of thyroid cancer which no longer possesses the functioning NIS symporter but can still produce thyroglobulin? First, one must continue TSH suppression, even though an increasing serum tg in the presence of a low TSH strongly suggests poor tumor responsiveness to suppression of this growth factor. There are, however, many clinicians who believe that more aggressive TSH suppression is required for high-risk disease and recurrent tumor, as documented
Serum tg Thresholds
Far more likely as causes of the TENIS syndrome presentation in FTC are microscopic remnants of normal tissue or of metastatic disease not visible with the diagnostic dosage of 131I, inadequate serum TSH stimulation, macroscopic metastatic disease that has mutated to lose NIS, or a combination of these factors. The physician must decide at what level of serum tg further investigation is necessary. The American Thyroid Association guidelines suggest level of stimulated tg >2 ng/mL as a
Tumor Detection
After excluding an antibody-induced false-positive tg assay and dilution of the iodine pool, the clinician must attempt to localize the site or sites of metastatic thyroid tissue if possible. A detailed review of the medical history and current systems should be undertaken and then a thorough physical examination. Metastases are most likely in lymph nodes of the neck but also are found not uncommonly in the lungs and bone. Metastatic FTC in lymph nodes of the neck may be detected by ultrasound
Surgical Resection
If there are suspicious nodal findings in the neck, surgical exploration and resection would follow before any consideration of systemic therapy, with its attendant side effects, would be considered.14 Lung metastases are generally multiple and therefore unresectable. However, especially in smokers, one must be aware that a synchronous bronchogenic carcinoma may be detected and tends to have a different, more spiculated pattern than metastases from thyroid cancer, and lung cancer may be
Empiric High-Dose 131I
Whether the clinician has found resectable thyroid cancer that no longer concentrates diagnostic activities of radioiodine, or whether he or she is now confronted with a patient with the TENIS syndrome and no identifiable or resectable tumor, he or she should at least consider therapy with an empiric, high dose of 131I. To provide high-dose empiric therapy requires a dosimetric measure of that radioiodine activity that will give the patient's bone marrow no more than 2 Gy, a radiation dose
External Beam Radiation Therapy
External beam radiotherapy (XBRT) has only a limited role in metastatic thyroid cancer in the neck. The tumor is not very radiosensitive, and radiotoxicity to the trachea and spinal cord, which are often adjacent to neck metastases, is dose-limiting. Doses in the range of 65-70 Gy are employed when invasive, partially unresectable thyroid cancer involves the trachea, esophagus, or other extrathyroidal sites in the neck because microscopic residual tumor is usually still present. Other
Chemotherapy
Standard chemotherapeutic agents, for example, doxorubicin, multiple doxorubicin and epirubicin combinations, cisplatin, and several taxanes, have an unimpressive record of efficacy, with limited partial responses (PR) up to 35%-40% and time to progression of only a few months, at the cost of considerable toxicity.24, 25, 26
In a trial of thalidomide involving 36 patients, of whom 28 were evaluable, there were 5 (18% PR) with a mean duration 4 months and 9 patients (32%) with stable disease,
Biological/Molecular Targeting Agents
The phrase “biological targeting agents” for cancer therapy is widely used, with the implication that this is a new concept for a different kind of therapeutic agent. In fact every form of chemotherapy has one or more membrane or intracellular targets. For example, doxorubicin targets and stabilizes the topoisomerase II complex, preventing the double helix of DNA from being resealed, thus blocking DNA replication. All the agents to be discussed in the subsections to follow are not unique in
Problems of Available Therapeutic Choices
Patients with the TENIS syndrome provide a therapeutic dilemma for which clear answers, based on randomized, double blind studies of various forms of therapy are lacking. In the currently active field of angiogenesis inhibitors in thyroid cancer, a review of 832 publications found no unbiased, double-blinded studies with clear endpoints and complete data.59 Few physicians who treat thyroid cancer have enough patients with the TENIS syndrome for a single-site double-blinded therapeutic study,
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