BACKGROUND: Malignant follicular lesion is not differentiated from benign lesions cytologically. The objective of this study was to assess the rate and the risk of malignancy in thyroid nodules which were cytologically diagnosed as follicular neoplasm by fine-needle aspiration (FNA) cytology. METHODS: All the patients who had undergone surgery with cytological diagnosis of follicular neoplasm from January 1996 through December 2001 in Asan Medical Center were studied retrospectively. Patients' and nodule characteristics were analyzed for factors associated with the presence of cancer. Two hundred and fifteen patients (196 females, 19 males) were included and their mean age was 39.4 years (range: 12~76). RESULTS: About half of the patients (102 out of 215, 47.4%) had malignancy with 29 papillary carcinomas, 57 follicular carcinomas, 15 H rthle cell carcinomas and 1 medullary carcinoma. Previously suggested factors associated with risk for malignancy, such as male gender, large tumor size (> 4 cm) or age of patients (> 45 years), were not associated with increased risk. Diagnosis of H rthle cell neoplasia on FNA was also not associated with increased risk. Only the extremes in age of the patients (below 20 or above 60 years) were associated with increased risk for malignancy. CONCLUSION: In our findings, prevalence of carcinoma in thyroid nodule patients with cytological diagnosis of follicular neoplasm was much higher than those reported. Clinical characteristics, such as male gender, age and nodule size, are not useful predictors for the presence of malignancy. Thyroid nodules with cytological diagnosis of follicular neoplasm warrant immediate surgery.
Adenocarcinoma, Follicular/pathology ; Adenoma, Oxyphilic/pathology ; Adolescent ; Adult ; Age Factors ; Aged ; Biopsy, Needle ; Carcinoma, Medullary/pathology ; Carcinoma, Papillary, Follicular/pathology ; Child ; Female ; Human ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Thyroid Neoplasms/*pathology ; Thyroid Nodule/*pathology ; Thyroidectomy ; Thyroiditis, Autoimmune/pathology

BACKGROUND: Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes. METHODS: We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-alpha, interleukin [IL]-1beta and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age). RESULTS: Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-kappaB expression in the skeletal muscle of OLETF rats. CONCLUSION: These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.
Animals ; Cytokines ; Diabetes Mellitus, Type 2 ; Down-Regulation ; Glucose ; Inflammation ; Insulin ; Insulin Resistance ; Interleukins ; Muscle, Skeletal ; NF-kappa B ; Phosphorylation ; Rats ; Rats, Inbred OLETF ; RNA, Messenger ; Stress, Physiological ; Thiazolidinediones

Osteopetrosis is a rare genetic bone disease characterized by increased bone density but prone to breakage due to defective osteoclastic function. Among two primary types of autosomal dominant osteopetrosis (ADO), osteopetrosis type II is characterized by sclerosis of bones, predominantly involving the spine, the pelvis, and the skull base. Fragility of bones and dental abscess are leading complications. This report presents a case of osteopetrosis in a 52-years-old female, which was complicated by the development of cavernous sinus thrombophlebitis and meningitis. She was suffered from multiple fractures since one year ago. Laboratory data revealed elevated serum levels of tartrate resistant acid phosphatase (TRAP) without carbonic anhydrase II DNA mutation. A thoracolumbar spine X-ray showed, typical findings of ADO type II (ADO II; Albers-Schonberg disease), prominent vertebral endplates so called the 'rugger jersey spine'. Her older sister also showed same typical spine appearance. We report a case of ADO II with cavernous sinus thrombophlebitis and meningitis that was successfully treated with long-term antibiotics with right sphenoidotomy.
Abscess ; Acid Phosphatase ; Anti-Bacterial Agents ; Bone Density ; Bone Diseases ; Carbonic Anhydrase II ; Cavernous Sinus Thrombosis* ; DNA ; Female ; Humans ; Meningitis* ; Osteoclasts ; Osteopetrosis* ; Pelvis ; Sclerosis ; Siblings ; Skull Base ; Spine

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays the role of a hypophysiotropic factor, which regulates the synthesis and secretion of pituitary hormones through the hypothalamo-hypophysial portal system. No clear evidence has yet been reported regarding the regulation of prolactin (PRL) by PACAP. In the present study, we tested a hypothesis that PACAP regulates the synthetic machinery of PRL during the estrus cycle and pubertal process using intracerebroventricular (i.c.v.) injection of an antisense oligodeoxynucleotide (ODN) against type I PACAP receptor (PAC1). METHODS: An RNase protection assay (RPA) was used to determine the pattern of hypothalamic PACAP and PAC1 mRNA expressions during the estrus cycle. Antisense PAC1 ODN was administered via i.c.v. injection to the female rats in normal estrus cycle of pubertal process. Northern blot analysis was used to determine the mRNA ievel of PRL in the pituitary gland. RESULTS: 1) PACAP mRNA in the medial basal hypothalamus was significantly increased at the diestrus I, while PAC1 mRNA showed no significant change. 2) PRL mRNA level of pituitary was increased by an injection of antisense PAC1 ODN at the proestrus and estrus stages. 3) PRL mRNA level of pituitary was significantly decreased by antisense PAC1 ODN injection at stage of prepuberty and initiate puberty, while its level was increased at stage of puberty. CONCLUSION: These data suggest that PACAP suppresses PRL mRNA synthesis through the PAC1 signaling pathway in the certain estrus cycle environments. It may be also involved in the regulation of pituitary PRL gene expression during the pubertal process
Adolescent ; Animals ; Blotting, Northern ; Diestrus ; Estrus ; Female* ; Gene Expression* ; Humans ; Hypothalamus ; Pituitary Adenylate Cyclase-Activating Polypeptide* ; Pituitary Gland* ; Pituitary Hormones ; Portal System ; Proestrus ; Prolactin* ; Puberty ; Rats* ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide ; Ribonucleases ; RNA, Messenger

Insulin autoimmune syndrome is an uncommon cause of hypoglycemia. According to the type of antibody, it can be classified as caused by insulin or insulin receptor autoantibodies. Generally, insulin autoimmune syndrome develops following exposure to exogenous insulin or sulfhydryl medications, although insulin or insulin receptor antibody may also occur spontaneously. We treated a 54-year-old woman who developed spontaneous hypoglycemia. The patient had repeated hypoglycemia despite the infusion of dextrose solution. Her serum insulin, c-peptide, and insulin autoantibody were elevated, even during the hypoglycemic periods. Insulin receptor autoantibody and HLA-cw4/B62/DR4 were positive. After steroid and diazoxide treatment, the hypoglycemic symptoms improved gradually. No further hypoglycemic episodes occurred after tapering the medication over 1 year. We present a case of insulin autoimmune syndrome with positive insulin and insulin receptor autoantibodies.
Autoantibodies ; C-Peptide ; Diazoxide ; Female ; Glucose ; Humans ; Hypoglycemia ; Insulin ; Middle Aged ; Receptor, Insulin

The course of painless thyroiditis is usually transient with a thyrotoxicosis phase that lasts for 2 months before recovery. Therefore, no treatment is required. This case is unusual because of the recurrence and severity of thyrotoxicosis, which required surgery of the thyroid gland to prevent a thyrotoxic crisis. A 43-year-old female who presented with severe thyrotoxicosis was found to have low radioactive iodine uptake, negative test results for TSH receptor antibodies, normal erythrocyte sedimentation rate and diffuse goiter without pain or tenderness; these findings suggested a diagnosis of painless thyroiditis. She was treated for relapsed painless thyroiditis for 10 years. However, in May 2014, she developed recurrent painless thyroiditis with severe thyrotoxicosis; free T4 41.5 ng/dL, TSH <0.005 mlU/mL. Owing to the severity and recurrence of thyrotoxicosis, total thyroidectomy was performed to prevent a thyrotoxic storm.
Adult ; Antibodies ; Blood Sedimentation ; Diagnosis ; Female ; Goiter ; Humans ; Iodine ; Receptors, Thyrotropin ; Recurrence ; Thyroid Crisis ; Thyroid Diseases ; Thyroid Gland* ; Thyroidectomy* ; Thyroiditis* ; Thyrotoxicosis

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. RESULTS: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.
Apoptosis* ; Blotting, Western ; Cadherins ; Caspase 3 ; Cell Survival ; Down-Regulation* ; Drug Resistance ; Drug Therapy ; Endothelial Growth Factors ; Flavonoids ; Humans ; Microscopy, Fluorescence ; Microtubules ; Neoplasm Metastasis ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Sirolimus ; Thyroid Carcinoma, Anaplastic* ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A

PURPOSE: There are many reports that diagnostic accuracy of fine needle aspiration (FNA) of thyroid is improved with ultrasound guidance, especially for impalpable nodules. Despite its general acceptance, routine use of ultrasound guided fine needle aspiration (USGFNA) has been the source of much controversy due to the lack of large-scale studies and lack of data on the natural course of welldifferentiated thyroid cancer of small size. METHODS: The aim of our study was to define the rate of malignancy in relatively large numbers of patients with incidentally detected impalpable thyroid nodules and to assess the extent of disease in patients with suspicious or malignant cytology on USGFNA of thyroid nodules by surgery. We retrospectively reviewed the medical records of the 267 patients who underwent USGFNA of incidental thyroid nodules from January 2000 through December 2001. RESULTS: Three hundred and seventeen nodules from 267 patients were aspirated. The average size of nodules was 0.9±0.3 cm, a range of 0.2 cm to 1.5 cm. All 317 lesions were impalpable. Cytological diagnosis included 101 inadequate specimen (32%), 139 benign (44%), 29 indeterminate (9%), 4 suspicious of follicular or Hrthle cell neoplasm (1%), 42 papillary carcinoma (13%), and 2 others. The size of the nodule was not related to the probability of getting an adequate specimen for cytological diagnosis. Forty of 48 patients with suspicious or malignant cytology underwent surgery. All 35 patients with a cytological diagnosis of papillary carcinoma were confirmed to have papillary carcinoma on histological results. One of 3 patients with a cytological diagnosis of follicular neoplasm had a follicular carcinoma. In 36 patients with well-differentiated thyroid cancer, extrathyroidal extension was observed in 44% (16/36), regional lymph node metastasis was found in 50% (18/36), and multifocal tumors were found in 39% (14/36). CONCLUSION: The rate of malignancy in incidentally detected impalpable thyroid nodules was 12% in retrospective analysis of our patients. Among those, 69% (25/36) of patients had either extrathyroidal extension or regional node involvement and 39% had multifocal tumors at surgery. This suggests that the small size itself could not guarantee a good prognosis in incidentally found thyroid cancers. USGFNA is a useful diagnostic method in those patients.
Aspirations (Psychology)* ; Biopsy, Fine-Needle ; Carcinoma, Papillary ; Diagnosis ; Humans ; Lymph Nodes ; Medical Records ; Methods ; Needles* ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography

Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). Impaired glucose tolerance is present in about 20-40% of acromegaly, with diabetes mellitus developing in about 10~15% of patients, but diabetic ketoacidosis is a rare association. Herein is reported a case of diabetic ketoacidosis in a 33 year-old female, with a 4 year history of typical acromegaly features. She presented with severe hyperglycemia and ketoacidosis, but with no other cause for this metabolic derangement. She had elevated plasma GH (50 ng/mL) and IGF-1 (1533 ng/mL) levels, and a pituitary macroadenoma. About 200 units of insulin per day were required for her glycemic control. However, the serum IGF-1 level and daily insulin requirement were significantly tapered after a transsphenoidal adenomectomy and long acting somatostatin analogue treatment. There was a good correlation with the daily insulin requirement and plasma IGF-1 level. This case demonstrates that severe GH excess can cause diabetic ketoacidosis, and that its successful treatment improves glucose metabolism.
Acromegaly* ; Adult ; Diabetes Mellitus ; Diabetic Ketoacidosis* ; Female ; Glucose ; Growth Hormone ; Humans ; Hyperglycemia ; Insulin ; Insulin Resistance ; Insulin-Like Growth Factor I ; Ketosis ; Metabolism ; Plasma ; Somatostatin

Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). Impaired glucose tolerance is present in about 20-40% of acromegaly, with diabetes mellitus developing in about 10~15% of patients, but diabetic ketoacidosis is a rare association. Herein is reported a case of diabetic ketoacidosis in a 33 year-old female, with a 4 year history of typical acromegaly features. She presented with severe hyperglycemia and ketoacidosis, but with no other cause for this metabolic derangement. She had elevated plasma GH (50 ng/mL) and IGF-1 (1533 ng/mL) levels, and a pituitary macroadenoma. About 200 units of insulin per day were required for her glycemic control. However, the serum IGF-1 level and daily insulin requirement were significantly tapered after a transsphenoidal adenomectomy and long acting somatostatin analogue treatment. There was a good correlation with the daily insulin requirement and plasma IGF-1 level. This case demonstrates that severe GH excess can cause diabetic ketoacidosis, and that its successful treatment improves glucose metabolism.
Acromegaly* ; Adult ; Diabetes Mellitus ; Diabetic Ketoacidosis* ; Female ; Glucose ; Growth Hormone ; Humans ; Hyperglycemia ; Insulin ; Insulin Resistance ; Insulin-Like Growth Factor I ; Ketosis ; Metabolism ; Plasma ; Somatostatin