Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Comparison of the Efficacy and Safety of Insulin Detemir Administered Once Daily According to Two Titration Algorithms (3-0-3 and 2-4-6-8) in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: This study was conducted to compare glycaemic control with insulin detemir administered according to two titration algorithms (3-0-3 and 2-4-6-8) after 20 weeks of treatment in subjects with type 2 diabetes mellitus inadequately controlled on metformin. METHODS: This was a 20-week, randomised, multicentre, open-labelled, treat-to-target trial. Forty-six patients were randomised in a 1:1 manner to either the 3-0-3 (G3, n=23) or 2-4-6-8 (G2, n=23) algorithm. The primary endpoint was change of haemoglobin A1c (HbA1c), and the secondary safety endpoint included hypoglycaemic events. RESULTS: After 20 weeks, HbA1c decreased similarly in the G3 and G2 groups, with a mean change of -0.9% from baseline. The mean change in fasting plasma glucose was numerically similar in both groups. The hypoglycaemia event rate per 100-patient-years of exposure (r) in the G2 group (r=1,427) was higher than that in the G3 group (r=807). CONCLUSION: Both treatment groups had numerically similar HbA1c reductions. A trend towards fewer hypoglycaemia episodes after dose stabilisation was seen with the simpler G3. Clinically, this may be an important observation, as a simpler titration algorithm may support self-management and maintenance of insulin therapy.

Adefovir-induced Fanconi syndrome associated with osteomalacia.

Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia.

Preoperative serum thyroglobulin and changes in serum thyroglobulin during TSH suppression independently predict follicular thyroid carcinoma in thyroid nodules with a cytological diagnosis of follicular lesion.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) cannot distinguish a follicular thyroid carcinoma (FTC) from a follicular adenoma in follicular lesions. We designed this study to determine whether the preoperative thyroglobulin (Tg) and change in serum Tg during thyroid-stimulating hormone (TSH) suppression can predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion. METHODS: Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed. Predictive factors for malignancy were evaluated using multivariate logistic regression models. Subgroup analyses of patients with TSH suppression therapy by levothyroxine were also conducted. RESULTS: Thirty-two patients (16%) had FTC, and 166 patients had confirmed benign nodules. The median preoperative serum Tg levels were significantly higher in patients with FTC compared to those with benign pathology (449 vs. 34 ng/mL, p < 0.001). The serum Tg (odds ratios (OR) 10.311, p < 0.001) and tumor volume (OR 4.500, p = 0.035) were found to be independent predictors for FTC in all patients with a cytological diagnosis of follicular lesion. Forty-eight patients received TSH suppression therapy. When we performed subgroup analyses on the patients with TSH suppression therapy, decrease less than 15% in serum Tg during TSH suppression was found to be an independent predictor of FTC (OR 13.918, p = 0.018). CONCLUSION: Preoperative serum Tg and changes in serum Tg during TSH suppression independently predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion.

The Usefulness of the Glycosylated Hemoglobin Level for the Diagnosis of Gestational Diabetes Mellitus in the Korean Population.

BACKGROUND: An oral glucose tolerance test (OGTT) is the current method used for screening and diagnosis of gestational diabetes mellitus (GDM). OGTT is a relatively complicated procedure and is expensive. Thus, new strategies that do not require fasting or more than a single blood draw may improve the diagnosis of GDM and increase the rate of GDM testing. We investigated the utility of monitoring glycosylated hemoglobin (HbA1c) levels for the diagnosis of GDM. METHODS: The data from 992 pregnant women with estimated gestational ages ranging from 24 to 28 weeks were retrospectively reviewed. There were 367 women with plasma glucose levels ≥140 mg/dL 1 hour after a 50-g OGTT. GDM was diagnosed according to the Carpenter-Coustan criteria for a 3-hour 100 g OGTT. A HbA1c assessment was performed at the same time. RESULTS: We enrolled 343 women in this study, and there were 109 women with GDM. The area under the curve the receiver operating characteristic curve for HbA1c detection of GDM was 0.852 (95% confidence interval, 0.808 to 0.897). A HbA1c cutoff value ≥5.35% had maximal points on the Youden index (0.581). The sensitivity was 87.2% and the specificity was 70.9% for diagnosing GDM. A threshold value ≥5.35% indicated that 163 patients had GDM and that 68 (41.7%) were false positive. The positive predictive value was 58.3% at this threshold value. CONCLUSION: Despite substantial progress in methodology, HbA1c values cannot replace OGTT for the diagnosis of GDM.

Retroperitoneal Bronchogenic Cyst Presenting Paraadrenal Tumor Incidentally Detected by (18)F-FDG PET/CT.

A follow-up (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scan of a 57-year-old asymptomatic male who had undergone total thyroidectomy for thyroid cancer revealed a 5.0 × 4.0-cm, well-defined, ovoid-shaped mass around the left adrenal gland without definite FDG uptake. On the adrenal CT scan, the left paraadrenal tumor showed high attenuation on the precontrast scan without enhancement. The average Hounsfield unit (HU) was 58.1 on the precontrast scan and 58.4 on the postcontrast scan. The patient underwent laparoscopic adrenalectomy for resection of the left paraadrenal tumor. The final histopathologic examination revealed a bronchogenic cyst. Although retroperitoneal bronchogenic cysts are rare, they should be considered in the differential diagnosis of retroperitoneal cystic tumors. The preoperative diagnosis is difficult, but a contrast-enhanced CT scan or (18)F-FDG PET/CT scan may be useful for differentiating hyperattenuated cysts from other soft tissue masses.

Actinomyces-like organisms in cervical smears: the association with intrauterine device and pelvic inflammatory diseases.

OBJECTIVE: To investigate the incidence of actinomyces-like organisms in routine cervical smears of Korean women and to evaluate its association with the development of pelvic inflammatory disease (PID) in these women. METHODS: The results of cervical smears between 2011 and 2012 at a single university hospital were searched. If positive for actinomyces-like organisms, the medical record of the patient was searched and development of PID was followed. If the data were not available in the medical record, the patient was contacted by telephone. RESULTS: The incidence of actinomyces-like organisms in cervical smears was 0.26% (52/20,390). Forty-two women (80.8%) were intrauterine device (IUD) users: the copper-IUD in 25 women and the levonorgestrel-releasing intrauterine system in 13 women (type unknown in 4 women). The majority (71.4%, 30/42) of the IUD users maintained the IUD. Prophylactic antibiotics were prescribed to 12 women. Two continuous IUD users were later diagnosed with PID, but these cases were not pelvic actinomycosis. CONCLUSION: It would be a reasonable option to choose the expectant management for asymptomatic women who incidentally showed actinomyces-like organisms in their cervical smear.

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial.

BACKGROUND: There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN: The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION: This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION: Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803).

Endoscopic comparison of alendronate alone and the enteric-coated alendronate with calcitriol combination in postmenopausal Korean females.

BACKGROUND/AIMS: This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 µg) combined drug (Maxmarvil, Yuyu Co.). METHODS: The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 ± 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. RESULTS: Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. CONCLUSIONS: The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.

Clinical utility of 18F-FDG PET/CT concurrent with 131I therapy in intermediate-to-high-risk patients with differentiated thyroid cancer: dual-center experience with 286 patients.

UNLABELLED: Patients with differentiated thyroid carcinoma (DTC) are treated with (131)I therapy after total thyroidectomy or surgical resection of recurrent tumor. However, some recurrent DTC lesions are not iodine-avid, which affects further treatment planning. The aim of this study was to evaluate the clinical benefit of (18)F-FDG PET/CT performed concurrently with (131)I therapy in DTC patients with intermediate to high risk. METHODS: We retrospectively enrolled 286 DTC patients at 2 Korean medical centers who comprised 2 different patient groups: 28 patients who underwent adjuvant (131)I treatment after curative surgical resection of recurrent tumor and 258 patients with intermediate to high risk who underwent (131)I ablation after total thyroidectomy. (131)I therapy and (18)F-FDG PET/CT scanning were performed on the same day. Administration of l-thyroxine was withheld from all enrollees for 4 wk before (131)I treatment. RESULTS: In 39 patients (14%), (18)F-FDG PET/CT detected additional recurrent or metastatic lesions that were not detected on the posttherapy (131)I scan, and the treatment plan was changed for 30 patients (10%) based on such findings. Among the 28 patients receiving (131)I treatment after resection of recurrent tumor, PET/CT detected additional lesions in 46%, and treatment was changed in 43%. Assessing a subgroup of stage T3-T4N1 patients with tumor size > 2.0 cm, among 258 patients undergoing (131)I ablation after total thyroidectomy, we found that 25% had additional positive PET/CT results, and treatment changed for 17%. In contrast, 8% of stage T3-T4N1 patients with tumor size ≤ 2.0 cm, 6% of stage T1-T2N1 patients, and 3% of stage T3-T4N0 patients had additional positive PET/CT findings. CONCLUSION: (18)F-FDG PET/CT performed concurrently with (131)I therapy detected additional lesions in 14% of DTC patients and was particularly helpful for detecting additional lesions in patients undergoing (131)I therapy after resection of recurrent tumor or in stage T3-T4N1 patients with tumor size > 2.0 cm.

BRAF (V600E) mutation analysis in papillary thyroid carcinomas by peptide nucleic acid clamp real-time PCR.

BACKGROUND: Activating somatic mutation of the BRAF (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (32-87%) in different series by different methods. The BRAF (V600E) mutation is associated with various clinicopathological parameters. The mutation is an important factor for the management of the PTC patients. The objective of this study was to detect the BRAF (V600E) mutation in PTCs by peptide nucleic acid (PNA) clamp real-time PCR and to analyze the results with clinicopathological parameters. METHODS: We performed genetic analysis of BRAF (V600E) by PNA clamp real-time PCR in 211 PTCs in Korea, stratified by clinicopathological parameters. RESULTS: The BRAF (V600E) mutation was detected in 90% of PTC cases, and it occurred significantly more often in female patients than in male patients (p = 0.001). The clinicopathological parameters of age, tumor size, and disease stage were not associated with the BRAF (V600E) mutation, while extrathyroid invasion (p = 0.031), lymph nodal metastasis (p = 0.002), and tumor multiplicity (p = 0.020) were. CONCLUSIONS: The prevalence (90%) of the BRAF (V600E) mutation in this study is the highest ever reported, confirming the key role of this mutation in PTC tumorigenesis. The BRAF (V600E) mutation was associated with aggressive clinical behaviors including extrathyroid invasion, lymph nodal metastasis and tumor multifocality. The PNA clamp real-time PCR method for the BRAF (V600E) mutation detection is sensitive and is applicable in a clinical setting.

DNA methylation of RUNX3 in papillary thyroid cancer.

BACKGROUND/AIMS: The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers. METHODS: We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC). RESULTS: RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines. CONCLUSIONS: We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

A case of idiopathic granulomatous hypophysitis.

Granulomatous hypophysitis is a rare pituitary condition that commonly presents with enlargement of the pituitary gland. A 31-year-old woman was admitted to the hospital with a severe headache and bitemporal hemianopsia. Magnetic resonance imaging (MRI) showed an 18 × 10-mm sellar mass with suprasellar extension and compression of the optic chiasm. Interestingly, brain MRI had shown no abnormal finding 4 months previously. On hormonal examination, hypopituitarism with mild hyperprolactinemia was noted. The biopsy revealed granulomatous changes with multinucleated giant cells. We herein report this rare case and discuss the relevant literature.

Aldosterone-producing adrenocortical carcinoma without hypertension.

Although adrenocortical tumors are common, adrenocortical carcinomas are rare. Moreover, aldosterone-producing adrenocortical carcinomas without hypertension are exceedingly rare, with only two previously reported cases.

MRI features of skeletal muscle lymphoma.

OBJECTIVE: The purpose of this study was to assess the MRI findings of skeletal muscle lymphoma. MATERIALS AND METHODS: MR images of pathologically proven lymphoma of skeletal muscle in 20 patients were retrospectively reviewed for the presence or absence of individual imaging findings. Nine patients had primary muscle lymphoma, and 11 patients had muscle metastasis from systemic lymphoma. RESULTS: The initial manifestation of skeletal muscle lymphoma was a muscle mass in 15 patients (75%) and abnormal muscle signal intensity in five patients (25%). Muscle enlargement was found in all cases. Long segmental involvement with orientation of the tumor along muscle fascicles was found in 15 patients (75%). Seventeen patients (85%) had traversing vessels within involved muscles. All of the tumors had equal to slightly increased signal intensity compared with normal muscle on T1-weighted images and intermediate signal intensity compared with fat on T2-weighted images. Among the 19 patients who underwent contrast-enhanced imaging, skeletal muscle lymphoma exhibited diffuse homogeneous enhancement in 13 patients (68%), predominantly peripheral thick bandlike enhancement in four patients (21%), and marginal septal enhancement in two patients (11%). Thick irregular enhancement of both deep and superficial fascia was found in 16 patients (84%), and one patient (5%) had deep enhancement only. Subcutaneous stranding was found in 16 patients (80%) and skin thickening in four patients (20%). CONCLUSION: Skeletal muscle lymphoma has distinctive MRI features that help differentiate it from other soft-tissue tumors and tumorlike lesions.

Resistance to thyroid hormone with missense mutation (V349M) in the thyroid hormone receptor beta gene.

Resistance to thyroid hormone (RTH) is a syndrome characterized by reduced sensitivity to the thyroid hormone. It is generally caused by mutations in the thyroid hormone receptor beta (TR beta) gene. On the basis of its clinical features, two different forms of this syndrome have been described: generalized resistance and pituitary resistance. A total of 122 TR beta gene mutations have been identified thus far. A 38-year-old woman presented with intermittent palpitation. Thyroid function tests revealed elevated levels of free T4 and TSH. TSH a-subunit levels were 0.41 mlU/mL, and magnetic resonance images of the sellar region evidenced no abnormal findings. The TSH response to TRH stimulation was found to be normal. The sequence analysis of the TR beta gene verified a missense mutation in exon 11, and the observed amino acid alteration was a substitution of a valine for a methionine at codon 349. We report the first case of a woman with RTH, which was found to be caused by a missense mutation (V349M) in the TR beta gene.

Mutation of Glu78 of the AVP-NPII gene impairs neurophysin as a carrier protein for arginine vasopressin in a family with neurohypophyseal diabetes insipidus.

Familial neurohypophyseal diabetes insipidus (FNDI; OMIM 192340) is a rare inherited disorder with an autosomal dominant inheritance pattern. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP). We report a Korean kindred in whom FNDI is associated with a novel deletion mutation in exon 2 of the AVP-NPII gene encoding the neurophysin II moiety. An 18-yr-old man with polyuria and polydipsia was shown to have central diabetes insipidus by using the water deprivation test. Four family members were suspected to have symptomatic vasopressin-deficient diabetes insipidus. Direct sequencing of the AVP-NPII gene showed a heterozygous GAG deletion mutation in exon 2, which results in in-frame deletion of glutamic acid (c.232_234delGAG; p.Glu78del). The mutation was predicted to yield an abnormal AVP precursor lacking Glu78 (E78) in its neurophysin II moiety. Because Glu78 is essential for neurophysin II molecules to form a salt bridge with AVP, the function of neurophysin as a carrier protein for AVP would be impaired. The proband's mother and sister have the same mutation. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the appropriate expression of vasopressin.

Increased expression of focal adhesion kinase in thyroid cancer: immunohistochemical study.

Focal adhesion kinase (FAK) is a tyrosine kinase that is found in cellular structures called focal adhesions. FAK appears to be a key element in signal transduction pathways involved in cell adhesion and locomotion. FAK is overexpressed in various tumors, including tumors derived from regions of the head and neck, colon, breast, prostate, and liver. In this study, we investigated immunohistochemically whether FAK expression was increased in thyroid cancers. FAK staining was not seen in any of the 20 normal thyroid tissues or the 6 nodular hyperplasia specimens. In contrast, FAK staining was observed in all of 17 papillary carcinomas, 9 follicular carcinomas, 8 medullary carcinomas, and 2 anaplastic carcinomas. Nine of 17 follicular adenomas showed FAK immunoreactivity. FAK was not expressed in normal tissue and nodular hyperplasia, but was expressed in some of the follicular adenoma, and all of the follicular, papillary, medullary and anaplastic thyroid carcinoma. This result indicates that the up-regulation of FAK may play a role in the development of thyroid carcinogenesis.

Immunohistochemical expression of COX-2 in thyroid nodules.

BACKGROUND: Recent evidence indicates that elevated COX-2 expression is associated with the carcinogenesis of numerous neoplasms. In this study, we investigated COX-2 expression in various thyroid specimens in order to elucidate its physiological role in pathologic conditions, and to evaluate the efficiency of COX-2 protein expression as a molecular marker of malignancy in the thyroid gland. METHODS: COX-2 expression was studied immunohistochemically in 19 papillary carcinomas, 8 follicular carcinomas, 14 follicular adenomas, 2 Hürthle cell carcinomas, 4 Hürthle cell adenomas, 8 nodular hyperplasias, 3 Graves' diseases, 3 Hashimoto's thyroiditis, 2 medullary carcinomas, 1 anaplastic carcinoma, and 20 normal thyroid tissues. RESULTS: COX-2 staining was not seen in any of the normal thyroid, Graves' disease, or nodular hyperplasia specimens. In contrast, COX-2 staining was observed in all of papillary carcinomas, Hashimoto's thyroiditis, Hürthle cell carcinomas, and Hürthle cell adenomas tissues. Moreover, 7 of 8 follicular carcinomas and 11 of 14 follicular adenomas showed COX-2 staining. CONCLUSION: These results indicate that COX-2 is not useful as a marker of malignancy. Since COX-2 expression was evident in follicular adenomas and in papillary and follicular carcinomas. Thus, the enzyme may be involved in the early process of thyroid tumorigenesis.