Objectives. Thyroid nodules are very prevalent in the adult population. Most of them are benign without affecting thyroid function; rarely, they are autonomous causing hyperthyroidism. Unfavourable nature of thyroid nodules is related to their malignant nature, which is established in 7−15%, or to the nodule growth, which may occur in one-third of benign thyroid nodules. They may occur in patients with thyroid autoimmune disease which is prevalent and associated with increased risk of thyroid cancer.
The diagnostic tools, including grey-scale ultrasound (US), US guided fine needle biopsy or thyroid scintigraphy, are not always reliable. None of them enables identification of benign nodules that will exhibit future growth and local problems. The opinion on the role of the laboratory tests such as Tg or calcitonin differs, and the role of more recent diagnostic tools, such as spectral Doppler sonography and elastography, still needs to be established. The recognition of imaging and laboratory markers that would help to predict unfavourable nodule nature would assure timely management of these patients and prevent unnecessary investigations of those with favourable nodule nature. The objective of the proposed research is to identify such markers. It will be achieved through the four specific objectives:
Objective 1: To evaluate the growth potential of unsuspicious thyroid nodules in adult Slovenian patients with known history of thyroid nodule.
Objective 2: To investigate the imaging and laboratory markers related to the nature of the nodule and surrounding thyroid tissue in patients with newly diagnosed thyroid nodules.
Objective 3: To determine predictive imaging and laboratory markers that influence thyroid nodule growth in patients with unsuspicious nodules.
Objective 4: To assess the impact of thyroid function and associated autoimmune thyroid disease on the nature and growth of thyroid nodules.
Methods. To achieve Objective 1, 200 patients with one or more nodules, first evaluated 5 or 10 years ago, will be invited to the study. We will perform US evaluation of nodule growth and characteristics and evaluate the predictive value of laboratory markers at initial examination (TSH, Tg). In order to achieve Objectives 2, 3 and 4, 300 adult patients will be included, in whom a comprehensive diagnostics will be done that will include a US assessment, qualitative (pattern of blood supply) and quantitative (measurement of the peak systolic velocity and resistance index) measurement of the blood flow in nodule and paranodular tissue. Elasticity of the nodule will be determined. We will perform thyroid scintigraphy and measure TSH, free thyroid hormones, antibodies, Tg and calcitonin. We will compare the characteristics of unsuspicious, autonomous and suspicious nodules. In patients with unsuspicious nodules, we will repeat the US assessment and measurements of TSH and Tg after 6 months and 1 year, and compare imaging and laboratory markers with respect to nodule growth. In patients with autoimmune thyroid disease, we will determine whether the imaging and laboratory characteristics of the nodule differ from subjects without autoimmune disease.
Expected results. Objective 1: We expect that nodule growth will occur in less than one third of subjects and will be mainly related to nodule size, TSH and Tg at initial examination. Objective 2: We assume that patients with a suspicious nodules will have a significantly higher nodule elasticity index and a higher TSH and Tg, and in patients with thyroid autonomy we expect significant increase in nodule vascularisation and higher Tg. Objective 3: We assume that patients with growing nodules will have a higher nodule volume at the initial presentation, a higher elasticity index and higher TSH and Tg. Objective 4: In patients with autoimmune thyroid disease we expect increased nodule vascularity and elasticity index as well as a higher TSH, a lower ratio of free hormones and a higher Tg.