This thesis describes clinical and fundamental studies addressing clinical challenges in patients with differentiated thyroid carcinoma (DTC). The diagnosis of DTC is hampered by the fact that... Show moreThis thesis describes clinical and fundamental studies addressing clinical challenges in patients with differentiated thyroid carcinoma (DTC). The diagnosis of DTC is hampered by the fact that although the incidence is low thyroid nodules are prevalent. In this thesis, the diagnostic value of a potential marker for DTC has been studied. Unfortunately, in a high proportion of patients with metastases of DTC, the tumor has become resistant to RAI therapy. We have performed fundamental studies into the mechanisms of the regulation of the sodium iodide symporter (NIS) that may have implications for restoring susceptibility to RAI therapy. Furthermore, the long-term efficacy of a new treatment with the multi kinase inhibitor (MKI) sorafenib for DTC patients with metastases that are unresponsive to RAI has been evaluated. Therapy with MKI has numerous adverse effects, including hypothyroidism. We have evaluated a potential mechanism of sorafenib associated hypothyroidism. Finally, DTC patients have traditionally been treated with TSH suppressive levothyroxine substitution. However, high thyroid hormone concentrations may have adverse effects on various organ systems, including the heart. In this thesis, we studied the effects of various thyroid hormone concentrations on cardiac function in DTC, using dedicated cardiac ultrasound. Show less
The first chapters of this thesis describe the treatment of radioiodine non-avid thyroid carcinoma with the tyrosine kinase inhibitor sorafenib. The remainder of the thesis describes the clinical... Show moreThe first chapters of this thesis describe the treatment of radioiodine non-avid thyroid carcinoma with the tyrosine kinase inhibitor sorafenib. The remainder of the thesis describes the clinical consequences of the treatment of thyroid carcinoma. Show less
Patients with DTC are initially treated with a total thyroidectomy and radioiodine therapy. Hereafter, all patients are treated with high doses of thyroxin aiming at significantly suppressing... Show morePatients with DTC are initially treated with a total thyroidectomy and radioiodine therapy. Hereafter, all patients are treated with high doses of thyroxin aiming at significantly suppressing thyrotropin (TSH) levels, resulting in a subclinical hyperthyroid state. The rationale of this approach is based on the potential harmful effects of TSH on tumor recurrence. Furthermore, thyroxin replacement therapy can be transiently stopped in these patients to detect residual or recurrent disease by TSH stimulated thyroglobulin levels. As a result of this standardized procedure, patients become overtly hypothyroid. In this thesis, questions about the clinical consequences of exogenous subclinical hyperthyroidism and hypothyroidism on bone metabolism, glucose metabolism, the autonomic nervous system and quality of life in patients with DTC are addressed. Show less
Differentiated thyroid carcinoma (DTC) has favorable prognosis with high cure rate under treatment of thyroidectomy followed by radiotherapy. However, therapeutic efficiency decreases when... Show moreDifferentiated thyroid carcinoma (DTC) has favorable prognosis with high cure rate under treatment of thyroidectomy followed by radiotherapy. However, therapeutic efficiency decreases when dedifferentiation occurs. One of the purposes in this study is to use pharmaceuticals intervention to promote therapeutic responsiveness in thyroid carcinomas. Lithium compound and retinoid derivatives have been applied in thyroid cancer patients and in normal and thyroid cancer cell lines. The results indicate that Lithium compound doesn__t influence either iodine uptake in vivo and in vitro conditions or iodine efflux in cell lines observed. Retinoid, Bexarotene, slightly increases iodine uptake in thyroid cancer patients but does not reach the therapeutic level. In attempt to find efficient diagnostic markers, 156 patient samples including subsets of thyroid carcinomas and benign thyroid disorders have been investigated using immunohistochemistry in tissue micro-array sections. The results indicate that combination of protein expression of NIS, FN and Gal-3 may distinguish benign tumors from malignant thyroid carcinomas with high accuracy. As thyroid cancer patients have high survival rate, efficient and sensitive screening tool is crucial for follow up in DTC. In this study, thyroglobulin (Tg) of over 600 patients has been studies at unicenter with uniformed treatment. The results prove that multiple tests of Tg at fix time points may predict DTC prognosis and death. Show less
