Thyroid cancer management: from a suspicious nodule to targeted therapy.

Thyroid nodules are very common, and their frequency is four to five times higher in women than in men. Most of them are benign, with only a very little percentage revealing a malignant neoplasm. About 50% of thyroid nodules are detected by self-palpation of neck, whereas the other 50% are diagnosed by neck ultrasonography and following fine-needle aspiration. Management of thyroid nodules is very difficult, because benign nodules are prevalent, whereas thyroid carcinoma is uncommon, representing only 1% of all malignancies. A standard diagnostic approach is represented by 'first-level' exams, consisting in neck ultrasonography and serum thyroid-stimulating hormone measurement, followed, only for nodules that are suspicious of malignancy, by 'second-level' exams, consisting of fine-needle aspiration and mutational test, which does detect particular DNA mutations present only in malignant cells. In this review, we will analyze the genetics of thyroid cancer and its heterogeneity, and we will briefly describe the current available diagnostic and therapeutic approaches.

Hyperthyroidism due to coexistence of Graves' disease and Struma ovarii.

OBJECTIVE: To report an unusual case of persistent thyrotoxicosis after treatment of Graves' disease, because of coexistence of struma ovarii. METHODS: We report the clinical history, imaging studies, laboratory and pathologic data, and treatment in a patient with persistent hyperthyroidism after surgical treatment of Graves' disease. In addition, we discuss some aspects of the pathogenesis of hyperthyroidism due to functioning struma ovarii. RESULTS: A 42-year-old woman underwent near-total thyroidectomy for treatment of Graves' disease. Post-operatively, hyperthyroidism was still present. Methimazole was administered again, and performance of a 131I whole-body scan demonstrated a focus of intense uptake in the pelvis. Pelvic ultrasonography revealed a mass (11 by 8 by 7.1 cm) arising from the right ovary, with both solid and cystic components. Abdominal surgical exploration was performed, and the final histologic diagnosis was struma ovarii. The symptoms of hyperthyroidism diminished, and 3 weeks postoperatively, the thyroid hormone levels were in the hypothyroid range. CONCLUSION: In patients with refractory hyperthyroidism after thyroid surgical treatment, radioiodine scanning should be performed to diagnose or exclude the functioning profile of ovarian masses.

New molecular targeted therapies in thyroid cancer.

Carcinoma of the thyroid gland is the most common malignancy of the endocrine system. Differentiated tumors are often curable with surgical resection and radioactive iodine. A small percentage of such patients, however, do not undergo remission and need new therapeutic approaches. Both anaplastic and medullary thyroid carcinomas exhibit aggressive behavior and are usually resistant to current therapeutic modalities. Thyroid carcinoma represents a fascinating model and a particularly promising paradigm for targeted therapy because some of the key oncogenic events are activating mutations of genes coding for tyrosine kinases, and these occur early in cancer development. A prototype is the RET proto-oncogene, a receptor tyrosine kinase, which is a key regulator of development and a 'hotspot' for oncogenic mutations. Mutations in the RET proto-oncogene have been identified as causative for papillary carcinoma and familial medullary thyroid carcinoma, making it an attractive target for selective inhibition in these subtypes. ZD 6474 has shown promising activity in preclinical models against RET kinase, and its contemporary inhibition of vascular endothelial growth factor and epidermal growth factor pathways renders it a very attractive drug for clinical trials in thyroid cancer. Activating point mutation of B-RAF can occur early in the development of papillary carcinoma. Moreover, papillary carcinomas with these mutations have more aggressive properties and are diagnosed more often at an advanced stage. Clinical evaluation of B-RAF-targeting drugs is undergoing and trials in thyroid cancer are planned. Agents that restore radioiodine uptake, such as histone deacetylase inhibitors and retinoids, represent another exciting field in new drug development in thyroid cancer.