Four kinds of hypothyroidism and the cancers of breast and lung found in cases of Japanese rheumatoid arthritis (RA), arthritis deformans, or bone fracture

Abstract

Japanese patients were selected from 875 patients who had undergone an orthopedic operation. Seventy-two cases of rheumatoid arthritis (RA) and 17 cases of suspected RA were analyzed. In parallel with high levels of rheumatoid factor (RF), Sjoegren syndrome, finger and toe deformans, and knee and hip arthritis deformans were observed at high frequencies. The arthritis deformans of 51 patients displayed a mean serum iron levels of 50 ± 33 (SD) μg/dl and transferrin saturation (TS) of 18 ± 11%. The hypothyroidisms diagnosed in the 12 patients were caused by autoimmune, hypopituitary, and papillary thyroid cancer (PTC). Two of the insulinoma cases had hypothyroidism due to down-regulated transcription of genes related to insulin. Two PTC, four breast ductal carcinomas, and three lung adenocarcinomas, which were observed in patients with bone diseases, were assumed to be caused by epidermal growth factor receptor (EGFR) gene mutations. One lung cancer with gefitinib-sensitive EGFR mutations, a breast cancer that expressed human epidermal growth factor receptor 2 (HER2), and a lung-metastasized popliteal epitheloid sarcoma showed disseminated bone and/or intra-lung metastases. When an HER2-positive breast cancer metastasized to the bones, TS was elevated to 73.4–81.4% with anemic attacks and high levels (12.4–16.8 ng/ml) of pyridinoline cross-linked carboxy-terminal telopeptide type I. In the other six cancer patients with noninvasive phenotypes, the metastases became cysts. One noninvasive lung cancer was confirmed to express thyroid transcription factor-1 (TTF-1). Polyps, varix, and multiple thromboses were found to be clinical signs of pre-EGFR cancers.