BACKGROUND AND OBJECTIVES: The BRAFV600E mutation has been regarded as the leading cause of papillary thyroid cancer (PTC). However, the multi-step carcinogenic process induced by BRAFV600E has been remained to be elucidated in thyroid gland. In this study, to investigate staged development of papillary thyroid carcinoma, we observed the histo-pathological findings of thyroid gland from BRAFV600E transgenic mice with a period of 60 weeks. MATERIALS AND METHODS: We histologically inspected 3, 9, 20, 27, 39, 44, 48 and 60 week old BRAFV600E transgenic mice derived from FVB/N background mice with a bovine thyroglobulin promoter which are providing thyroid specific BRAFV600E expression. RESULTS: Thyroid glands from 3 and 9 week old BRAFV600E transgenic mice were enlarged and showed abnormal histologic feature such as distorted follicular architectures. The 20 and 27 week old BRAFV600E transgenic mice showed irregularly enlarged thyroid gland sprouting out above the carotid arteries. Thyroid gland derived from 39 week old mice showed reduced formation of intact follicular structure and increased solid area. Thyroid glands were entirely replaced by firm tumor mass composed of poorly differentiated cell at 44 weeks. Interestingly, we could observe tracheal invasion, surrounding muscle invasion in thyroid gland from 48 week old mice and detect lung metastasis in 60 week old mice. CONCLUSION: Thyroid specific expression of BRAFV600E induced staged development of thyroid cancer. This finding may support that BRAFV600E have a role in entire carcinogenic process such as tumor initiation, development and progression.
Animals ; Carcinoma ; Carotid Arteries ; Lung ; Mice ; Mice, Transgenic ; Muscles ; Neoplasm Metastasis ; Proto-Oncogene Proteins B-raf ; Thyroglobulin ; Thyroid Gland ; Thyroid Neoplasms

No abstract available.
Carcinoma/*genetics ; Core Binding Factor Alpha 3 Subunit/*genetics ; Humans ; Thyroid Neoplasms/*genetics

A 56-year-old male with a gastrointestinal stromal tumor (GIST) underwent surgical resection of the tumor. Nine months after surgery, imatinib therapy was initiated because of the discovery of metastatic tumors in the left adrenal gland and in a lymph node of the peritoneum. Seventeen months later, the patient achieved complete remission (CR) and imatinib therapy was continued. However, 48 months after initiation of imatinib therapy, computed tomography scans revealed a left adrenal gland metastasis and the patient underwent left adrenalectomy. Immunohistochemical staining indicated that the spindle-shaped cells of the resected tumor were positive for C-kit, thus confirming metastasis of the GIST. This is the first report from Korea of an adrenal gland metastasis from a GIST. Worldwide, only two such cases have been reported. Here, we describe the first case of a distant recurrence of a GIST in the left adrenal gland after CR had been achieved with the aid of surgical resection and imatinib therapy.
Adrenal Glands* ; Adrenalectomy ; Gastrointestinal Stromal Tumors* ; Humans ; Imatinib Mesylate ; Korea ; Lymph Nodes ; Male ; Middle Aged ; Neoplasm Metastasis* ; Peritoneum ; Recurrence

Insulin resistance in patients with diabetes mellitus may be aggravated by various causes, including infection, obesity, and medications known to affect insulin sensitivity. During pregnancy, insulin resistance can be the result of hormones secreted by the placenta. Blood glucose control during pregnancy is important in preventing obstetric complications including miscarriage, congenital malformations, and macrosomia. We report a case of severe insulin resistance in an obese diabetic pregnant woman whose one-day insulin requirements were up to 1,000 IU.
Abortion, Spontaneous ; Blood Glucose ; Diabetes Mellitus ; Female ; Humans ; Insulin Resistance ; Insulin ; Obesity ; Placenta ; Pregnancy ; Pregnant Women

BACKGROUND: Statins are used to treat hypercholesterolemia; however, major cardiovascular events are decreased only 30% by statin treatment. Treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been reported to decrease serum glucose levels and improved insulin sensitivity in mice and humans, but there was no study in serum cholesterol levels. This study examined the effect of gefitinib, an EGFR tyrosine kinase inhibitor, on cholesterol metabolism in humans. METHODS: We retrospectively reviewed the medical records of 299 patients with primary lung cancer treated with gefitinib for ≥1 month and 72 patients with other treatments. Serum cholesterol, serum triglycerides, and body mass index were measured before and after treatment. The changes in serum cholesterol, serum triglycerides, and body mass index were compared between the gefitinib treatment group and the control group and were also analyzed according to the presence or absence of EGFR mutations. RESULTS: Serum cholesterol levels decreased significantly from 178.9 to 164.4 mg/dL after 1-month of gefitinib treatment. A total of 54 of the 299 patients underwent examination for the presence of the EGFR mutations. Serum cholesterol was significantly decreased in the group with the activating EGFR mutation (Δ=21.3 mg/dL) compared to that of those without the EGFR mutation (Δ=-3.1 mg/dL) after treatment with gefitinib. In contrast, there was no significantly difference between the two groups in control patients. CONCLUSION: Treatment with gefitinib decreased serum cholesterol in lung cancer patients, particularly in those with activating mutations in EGFR. These data suggest that EGFR tyrosine kinase inhibitors provide a novel and attractive strategy for the treatment of hypercholesterolemia.
Animals ; Blood Glucose ; Body Mass Index ; Cholesterol ; Epidermal Growth Factor ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Insulin Resistance ; Lung Neoplasms ; Lung ; Medical Records ; Metabolism ; Mice ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Triglycerides

BACKGROUND: Although both thyroid histology and serum concentrations of hormones are known to change with age, only a few reports exist on the relationship between the age-related structural and functional changes of the thyroid follicles in both mice and humans. Our objectives were to investigate age-related histological changes of the thyroid follicles and to determine whether these morphological changes were associated with the functional activity of the follicles. METHODS: The thyroid glands of mice at 18 weeks and at 6, 15, and 30 months of age were histologically examined, and the serum levels of thyroid hormones were measured in 11-week-old and 20-month-old mice. Samples of human thyroid tissue from 10 women over 70 years old and 10 women between 30 and 50 years of age were analyzed in conjunction with serum thyroid hormone level. RESULTS: The histological and functional changes observed in the thyroid follicles of aged mice and women were as follows: variable sizing and enlargement of the follicles; increased irregularity of follicles; Sanderson’s polsters in the wall of large follicles; a large thyroglobulin (Tg) globule or numerous small fragmented Tg globules in follicular lumens; oncocytic change in follicular cells; and markedly dilated follicles empty of colloid. Serum T3 levels in 20-month-old mice and humans were unremarkable. CONCLUSIONS: Thyroid follicles of aged mice and women show characteristic morphological changes, such as cystic atrophy, empty colloid, and Tg globules.
Aged ; Animals ; Atrophy ; Colloids ; Female ; Humans* ; Infant ; Mice ; Thyroglobulin ; Thyroid Gland* ; Thyroid Hormones

BACKGROUND: Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined. METHODS: A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records. RESULTS: Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome. CONCLUSION: Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome.
Blood Cell Count ; Blood Glucose* ; Cardiovascular Diseases ; Chungcheongnam-do ; Cushing Syndrome* ; Eosinophils* ; Glucose ; Glucose Intolerance ; Hemoglobin A, Glycosylated ; Humans ; Hydrocortisone ; Leukocytes ; Medical Records ; Pituitary ACTH Hypersecretion ; Retrospective Studies

Phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) is a common cause of X-linked hypophosphatemic (XLH) rickets. Diverse PHEX gene mutations have been reported; however, gene mutations in sporadic rickets are less common than in XLH rickets. Herein, we describe a 50-year-old female patient with sporadic hypophosphatemic rickets harboring a novel splicing-site mutation in the PHEX gene (c.663+1G>A) at the exon 5-intron 5 boundary. The patient had recently suffered from right thigh pain and an aggravated waddling gait. She also presented with very short stature, generalized bone pain, and muscle weakness. Despite low serum phosphate levels, her phosphate reabsorption rate was lower than normal. Additionally, her 1,25-dihydroxyvitamin D3 concentration was lower than normal, although FGF23 level was normal. After treatment with alfacalcidol and elemental phosphate, her rachitic symptoms subsided, and callus formation was observed in the fracture site on the right femur.
Bony Callus ; Calcitriol ; Endopeptidases ; Exons ; Female ; Femur ; Gait ; Humans ; Middle Aged ; Muscle Weakness ; Rickets ; Rickets, Hypophosphatemic* ; Thigh

BACKGROUND: Elevated serum levels of growth differentiation factor-15 (GDF-15) are associated with type 2 diabetes. Therefore, the effects of atorvastatin on metabolic parameters and GDF-15 levels in patients with type 2 diabetes and dyslipidemia were evaluated. METHODS: In this prospective randomized trial from February 2013 to March 2014, 50 consecutive type 2 diabetic patients with a low density lipoprotein cholesterol (LDL-C) levels > or =100 mg/dL were enrolled. The patients were divided into two groups based on the amount of atorvastatin prescribed, 10 mg/day (n=23) or 40 mg/day (n=27). The effect of atorvastatin on metabolic parameters, including lipid profiles and GDF-15 levels, at baseline and after 8 weeks of treatment were compared. RESULTS: The baseline metabolic parameters and GDF-15 levels were not significantly different between the two groups. After 8 weeks of treatment, the total cholesterol (TC) and LDL-C levels were significantly decreased in both groups. The mean changes in TC and LDL-C levels were more significant in the 40 mg atorvastatin group. The GDF-15 level was decreased in the 10 mg atorvastatin group, from 1,460.6+/-874.8 to 1,451.0+/-770.8 pg/mL, and was increased in the 40 mg atorvastatin group, from 1,271.6+/-801.0 to 1,341.4+/-855.2 pg/mL. However, the change in the GDF-15 level was not statistically significant in the 10 or 40 mg atorvastatin group (P=0.665 and P=0.745, respectively). CONCLUSION: The GDF-15 levels were not significantly changed after an 8-week treatment with atorvastatin in type 2 diabetic patients.
Cholesterol ; Cholesterol, LDL ; Diabetes Mellitus, Type 2* ; Dyslipidemias* ; Growth Differentiation Factor 15 ; Humans ; Prospective Studies ; Atorvastatin Calcium

BACKGROUND: The significance of adiponectin levels in elderly individuals with prediabetes has yet to be determined. Thus, the present study was performed to evaluate the relationships between adiponectin levels and anthropometric variables, body composition parameters, insulin sensitivity, and lipid profiles in elderly prediabetic patients. METHODS: The present study included 120 subjects with prediabetes who were >65 years of age and were selected from among 1,993 subjects enrolled in the Korea Rural Genomic Cohort Study. All subjects underwent a 75 g oral glucose tolerance test and tests for measurement of insulin sensitivity. All diagnoses of prediabetes satisfied the criteria of the American Diabetes Association. RESULTS: Plasma adiponectin levels were lower in elderly prediabetic subjects than elderly subjects with normal glucose tolerance (P<0.01) as well as in elderly prediabetic patients with metabolic syndrome (MetS) than in those without MetS (P<0.02). When the subjects were categorized into two groups according to plasma adiponectin levels, the waist-to-hip ratio and 2-hour insulin levels were significantly lower in individuals with high plasma adiponectin levels than in those with low plasma adiponectin levels. Additionally, the plasma adiponectin levels of elderly prediabetic subject were inversely correlated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels. CONCLUSION: The present findings demonstrated that the major factors correlated with adiponectin levels in elderly prediabetic subjects were BMI, WC, waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels.
Adiponectin* ; Aged* ; Body Composition ; Body Mass Index ; Cohort Studies ; Diagnosis ; Glucose ; Glucose Tolerance Test ; Humans ; Insulin ; Insulin Resistance ; Intra-Abdominal Fat ; Korea ; Plasma* ; Prediabetic State* ; Waist Circumference ; Waist-Hip Ratio