Therefore, screening by colonoscopy is recommended. In our study, colon cancer was found in five patients and was the second most frequent cancer. IGF-1 is an important factor for replication of normal thyroid follicular cells and reducing apoptosis. Increased IGF-1 stimulation may increase carcinogenesis and act with other initiating factors to promote progression of thyroid cancer from an occult to a clinically relevant stage. In a recent metaanalysis by Wolinski et al., thyroid cancer occur significantly more often in acromegalic patients than in general population, and a recent case-control study showed that thyroid cancer has a 10.21 increased risk in patients with acromegaly compared with that in a control group. In our study, the prevalence of PTC was 25% in patients with acromegaly, and uncontrolled acromegaly was significantly higher in frequency in the PTC group. Recent studies have reported that cancer incidence and cancer-related mortality rates are elevated in patients with persistent active disease. These results suggest that long-term stimulation by GH and IGF-1 from thyroid follicular cells may be Afatinib EGFR/HER2 inhibitor responsible for thyroid carcinogenesis in patients with acromegaly. IGF-1R is a hetero-tetrameric protein, consisting of two extracellular a-subunits that bind IGF and two transmembrane b-subunits bearing intrinsic tyrosine kinase activity. IGF-1 binds IGF-1R and activates the phosphatidylinositol-3 kinase and AKT/protein kinase B pathways and their phosphorylation, which are anti-apoptotic mechanisms that also activate the RAS/MEK/ MAPK pathway as a cellular differentiation, proliferation, senescence and survival mechanism. IGF-1R is overexpressed in tumors from several anatomical sites, including normal and malignant thyroid follicular cells. Several clinical and experimental studies have reported that increased circulating IGF-1 levels and increased expression of IGF-1 and IGF-1R in tumor tissues are involved in the development of these malignant tumors. In our study, IGF-1Rb was expressed by 100% of thyroid cancer cells and was stained more strongly in cancer tissue than in adjacent normal tissue, which is similar to a previous report. IGF-1Rb IHC staining in normal thyroid tissue adjacent to cancer tissue was significantly less intense in acromegalic PTC compared with that in non-acromegalic PTC. Increased serum IGF-1 levels in patients with acromegaly may downregulate IGF-1Rb; however, the autocrine and paracrine effects of IGF-1 can be induced by local expression of IGF-1Rb in tumor tissue. This may partly contribute to the abnormal growth of tumors, and is recognized as an attractive target for cancer treatment. PTCs frequently harbor an activating mutation of BRAFV600E. The BRAFV600E mutation suggests that ERK, a downstream effector of BRAF, may play a major role in the carcinogenesis of PTC, and is associated with extrathyroid invasion, lymph node metastases, advanced tumor stage, and frequent recurrence. Multi-kinase inhibitors such as sorafenib, which target vascular endothelial growth factor receptors 2 and 3, common RET/PTC subtypes, and BRAF, have shown great promise in the treatment of malignancies harboring a BRAFV600E mutation. However, the BRAFV600E mutation is rare in acromegalic patients with PTC, and these patients should be treated with an anti-IGF-1R therapeutic approach. Several limitations to our study should be mentioned. No control group for comparison of the prevalence of thyroid cancer in patients with acromegaly was included. The overall thyroid cancer prevalence is 76.9 and 427.5 per 100,000 in males and females, respectively in a 2011 study in Korea.