Clinical and laboratory follow-up in differentiated thyroid carcinoma.

Thyroid carcinoma is the most frequent endocrine malignant neoplasm even if a rare occurrence (0.5%-1.0%) of all human malignant tumors. Primary differentiated (papillary and follicular) forms represent over 90% of the total. Since recurrence of thyroid carcinoma can occur even after several years, patients must undergo a life-long follow-up. Thyroglobulin, being organ-specific, plays a major role as tumor marker and it is used essentially in the monitoring and follow-up of patients with differentiated thyroid carcinoma, both during L-thyroxine suppressive therapy and when it is discontinued or after recombinant TSH administration. The presence of antithyroglobulin antibodies masks the real value of thyroglobulin and therefore, at the same time, antithyroglobulin antibodies should always be determined.

Role of nuclear medicine in the diagnosis and therapy of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) originates in the parafollicular cells (C cells) of the thyroid, secreting both calcitonin and CEA. Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary palpable thyroid nodule and in most cases the definitive diagnosis is established only at the time of surgery. Nuclear medicine procedures, which play a minor role in the preoperative evaluation of MTC, are essential in postoperative follow-up to detect residual and/or recurrent tumor. A number of radiopharmaceuticals are able to visualize MTC lesions with considerable advantages in diagnosis and prognosis, some of them having also a therapeutic role. Among them, 99mTc[V]DMSA shows the highest diagnostic sensitivity and is considered by many authors the radiopharmaceutical of choice in the postoperative work-up of MTC. Radioiodinated MIBG, in spite of its high specificity has a poor sensitivity (30%); however it is useful for the identification of pheochromocytoma and, in patients showing MIBG uptake in tumoral lesions, high activities of 131I-MIBG may be used for therapy. 111In labeled octreotide detects lesions which express somatostatin receptors; a positive scintigraphic result seems to give also prognostic information (higher uptake in slow-growing lesions) and provides the basis for treatment with octreotide or lanreotide and 111In or 90Y-labeled octreotide analogues. Interesting perspectives are offered by 18F-FDG PET and monoclonal anti-CEA labeled antibodies; the latter may be also used for therapy.

Radioiodine therapy in differentiated thyroid carcinoma.

Radioiodine therapy has been successfully applied for over 50 years in the management of differentiated thyroid carcinoma. Careful patient preparation and selection of the optimal dose of radioiodine to be administered are two factors of major importance in the course of management. Main indications for 131I therapy are the ablation of residual thyroid tissue after thyroidectomy, the treatment of locoregional recurrence and distant metastases which involve almost exclusively the lung and bones. A controversial aspect is that of patients with high serum TG levels but negative whole body 131I scintigraphy for whom there is no general agreement. Other controversial aspects involve ablation therapy as the selection of patients to be treated and the control of its efficacy. The cost and possible adverse side-effects of 131I therapy require a careful analysis of prognostic factors in each patient candidate for the treatment.

Diagnostic imaging in thyrotoxicosis.

In thyrotoxicosis, imaging mainly scintigraphy, color Doppler sonography and radioiodine uptake test are used in the differential diagnosis as well as in the morphofunctional evaluation of the thyroid before and after therapy (mainly pharmacological or with radioiodine). Radioiodine uptake test differentiates high uptake thyrotoxicosis (Graves'disease, toxic nodular goiter) and low uptake thyrotoxycosis (subacute or silent thyroiditis, ectopic thyrotoxicosis, iodine-induced hyperthyroidism). In Graves'disease scintigraphy shows thyroid enlargement with intense homogeneous tracer uptake; rarely nodules with no uptake are present. On color Doppler sonography, a part from enlargement, typical findings are: diffuse structural hypoechogenicity (at times with echoic nodules), parenchymal hypervascularization ("thyroid inferno"), high systolic velocities (PSV > 70-100 cm/sec) in inferior thyroid arteries. Scintigraphy is the only method able to evidence an autonomously functioning thyroid nodule and stage it (in association to clinical findings and TSH, FT3, FT4 determination) as: toxic, non toxic (or pretoxic) and compensated, depending on whether there is inhibition of extranodular tissue. A scintigraphically "hot" nodule appears hypervascularized on color Doppler sonography (especially in the toxic or pre-toxic phase) with high PSV (> 50-70 cm/sec) in the ipsilateral inferior thyroid artery. The most reliable parameters in the evaluation of the therapeutic efficacy are: decreases in thyroid (Graves'disease) or nodular (autonomously functioning nodule) volume; decreased radioiodine uptake (Graves'disease); functional recovery of suppressed parenchyma (autonomously functioning nodule); decreased PSV in the inferior thyroid arteries.