PURPOSE: Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes. MATERIALS AND METHODS: This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007–2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1.73 m2. Lactic acidosis was defined as plasma lactate levels >5 mmol/L and arterial pH <7.35. RESULTS: Metformin was used in 61.4% of the patients with type 2 diabetes mellitus. Plasma lactate levels were not different in the patients with and without metformin use. There was no difference in prevalence of hyperlactatemia and lactic acidosis between the patients with and without metformin use (18.9% vs. 18.7%, p=0.905 for hyperlactatemia and 2.8% vs. 3.3%, p=0.544 for lactic acidosis). Similar results were observed in the patients with estimated glomerular filtration rate <60 mL/min/1.73 m². Most patients with lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicated no association between metformin use and lactic acidosis, whereas tissue hypoxia was an independent risk factor for lactic acidosis [odds ratio 4.603 (95% confidence interval, 1.327–15.965)]. CONCLUSION: Metformin use was not associated with hyperlactatemia or lactic acidosis in patients with type 2 diabetes.
Acidosis, Lactic* ; Anoxia ; Cross-Sectional Studies ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Glomerular Filtration Rate ; Humans ; Hydrogen-Ion Concentration ; Hyperlactatemia ; Lactic Acid* ; Metformin* ; Mortality ; Perfusion ; Plasma ; Prevalence ; Risk Factors

BACKGROUND: The relationship between dehydroepiandrosterone sulfate (DHEA-S) and bone mineral density (BMD) is controversial. And findings of most studies that have investigated this relationship are restricted to postmenopausal women. In this study, we investigated the relationship between serum DHEA-S and BMD in both men and women. METHODS: This cross-sectional study evaluated a total of 294 healthy Korean participants through a medical examination program. And a subgroup of 154 participants was subjected to a longitudinal analysis. We measured BMD by dual energy X-ray absorptiometry and assayed DHEA-S by a chemiluminescent immunoassay. RESULTS: We evaluated the association between serum DHEA-S concentration and BMD at the femur trochanter after adjusting for cofounders such as age, body mass index, lifestyle factors, serum cortisol level, serum insulin-like growth factor 1 (IGF-1) level, and sex. Through our longitudinal study, we found that the changes in BMD at the total spine, at the femur neck, and at the femur trochanter were all smaller in the ΔDHEA-S <0 group than in the ΔDHEA-S >0 group. CONCLUSIONS: We found that there was a positive correlation between serum DHEA-S and femur BMD, which suggests that controlling serum DHEA-S levels may retard age-related BMD reduction in Koreans.
Absorptiometry, Photon ; Aging ; Body Mass Index ; Bone Density* ; Cross-Sectional Studies ; Dehydroepiandrosterone Sulfate* ; Dehydroepiandrosterone* ; Female ; Femur ; Femur Neck ; Humans ; Hydrocortisone ; Immunoassay ; Life Style ; Longitudinal Studies ; Male ; Osteoporosis ; Spine

PURPOSE: It is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results. MATERIALS AND METHODS: We evaluated 214 patients who had undergone fine-needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated. RESULTS: Of 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and "diffuse thyroid disease" (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC. CONCLUSION: Suspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US.
Aged ; Aged, 80 and over ; Autoantibodies ; Biopsy, Fine-Needle/*methods ; Calcinosis ; Carcinoma/*pathology ; Female ; Hashimoto Disease ; Humans ; Hyperplasia/*pathology ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Retrospective Studies ; Sensitivity and Specificity ; Thyroglobulin/blood ; Thyroid Diseases ; Thyroid Neoplasms/*pathology ; Thyroid Nodule/*pathology ; Thyroiditis, Autoimmune/*pathology ; Thyrotropin/blood

Congenital adrenal hyperplasia (CAH) with 17alpha-hydroxylase/17,20-lyase deficiency is usually characterized by hypertension and primary amenorrhea, sexual infantilism in women, and pseudohermaphroditism in men. hypertension, and sexual infantilism in women and pseudohermaphroditism in men. In rare cases, a huge adrenal gland tumor can present as a clinical manifestation in untreated CAH. Adrenal cortical adenoma is an even more rare phenotype in CAH with 17alpha-hydroxylase/17,20-lyase deficiency. A 36-year-old female presented with hypertension and abdominal pain caused by a huge adrenal mass. Due to mass size and symptoms, left adrenalectomy was performed. After adrenalectomy, blood pressure remained high. Based on hormonal and genetic evaluation, the patient was diagnosed as CAH with 17alpha-hydroxylase/17,20-lyase deficiency. The possibility of a tumorous change in the adrenal gland due to untreated CAH should be considered. It is important that untreated CAH not be misdiagnosed as primary adrenal tumor as these conditions require different treatments. Adequate suppression of adrenocorticotropic hormone (ACTH) in CAH is also important to treat and to prevent the tumorous changes in the adrenal gland. Herein, we report a case of untreated CAH with 17alpha-hydroxylase/17,20-lyase deficiency presenting with large adrenal cortical adenoma and discuss the progression of adrenal gland hyperplasia due to inappropriate suppression of ACTH secretion.
Abdominal Pain ; Adrenal Glands ; Adrenal Hyperplasia, Congenital* ; Adrenalectomy ; Adrenocortical Adenoma ; Adrenocorticotropic Hormone ; Adult ; Amenorrhea ; Blood Pressure ; Disorders of Sex Development ; Female ; Humans ; Hyperplasia ; Hypertension ; Male ; Phenotype ; Sexual Infantilism

PURPOSE: The association between autoimmune thyroid diseases (AITDs) and vitamin D deficiency is controversial. We aimed to evaluate the relationship between serum 25-hydroxy-vitamin D3 [25(OH)D3] and anti-thyroid antibody levels. MATERIALS AND METHODS: 25(OH)D3, anti-thyroid antibodies, and thyroid function measured in 304 patients who visited the endocrinology clinic were analyzed. The patients were subgrouped into the AITDs or non-AITDs category according to the presence or absence of anti-thyroid antibodies. The relationship between anti-thyroid peroxidase antibody (TPOAb) and 25(OH)D3 was evaluated. RESULTS: The patients with elevated anti-thyroid antibodies had lower levels of serum 25(OH)D3 than those who did not (12.6+/-5.5 ng/mL vs. 14.5+/-7.3 ng/mL, respectively, p<0.001). Importantly, after adjusting for age, sex, and body mass index, a negative correlation (r=-0.252, p<0.001) was recognized between 25(OH)D3 and TPOAb levels in the AITDs group, but this correlation did not exist in the non-AITDs group (r=0.117, p=0.127). 25(OH)D3 level was confirmed as an independent factor after adjusting for co-factors that may affect the presence of TPOAb in the AITDs group. CONCLUSION: 25(OH)D3 level is an independent factor affecting the presence of TPOAb in AITDs. The causal effect of 25(OH)D3 deficiency to AITDs is to be elucidated.
Antibodies ; Body Mass Index ; Endocrinology ; Humans ; Methods ; Peroxidase* ; Thyroid Diseases ; Thyroid Gland ; Thyroiditis, Autoimmune* ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a familial syndrome characterized by the parathyroid, pancreas and pituitary tumors. Parathyroid tumors are the most common clinical manifestations, occurring in more than 90% of MEN1 patients. Heterozygous germline mutations of the MENIN gene underlie the tumorigenesis in MEN1 and epigenetic alterations along with germline mutations may contribute to tumorigenesis. Here, we investigated the associations between genotype and phenotype in Korean MEN1 patients. METHODS: We analyzed medical records from 14 unrelated MEN1 patients who had newly confirmed MENIN germline mutations, together with 14 previous reports in Korea. Aberrant DNA methylations were also examined in MEN1-related parathyroid tumors using the Infinium HumanMethylation 450 BeadChip. RESULTS: Total 28 germline mutations of MENIN were relatively highly concentrated in exons 7 and 8 compared to previous reports from Western countries. Six mutations (c.111dupT/p.S38Ffs*79, c.225_226insT/p.T76Yfs*41, c.383_398del16/p.S128Tfs*52, c.746dupT/p.H250Afs*20, c.1150G>T/p.E384*, and c.1508G>A/p.G503N) were newly found in the present study. Of interest, four patients (15%) showed unusual initial presentations and three patients were diagnosed incidentally at the general medical checkup. We also found three distinct sites in exon 2 of MENIN were significantly hypomethylated in the MEN1 parathyroid tumors, comparing correspondent blood samples. CONCLUSION: We also have found a lack of genotype/phenotype correlation in Korean MEN1 patients. There were not a few unusual initial manifestations in MEN1 patients, thus, genetic testing for the MENIN germline mutations can provide important information for the better prognosis. Further studies are warranted to investigate altered DNA methylations in the MENIN gene involved in tumorigenesis.
Carcinogenesis ; DNA Methylation ; Epigenomics* ; Exons ; Genetic Testing ; Genotype ; Germ-Line Mutation ; Humans ; Korea ; Medical Records ; Multiple Endocrine Neoplasia Type 1* ; Pancreas ; Phenotype ; Pituitary Neoplasms ; Prognosis

BACKGROUND: Patients with subclinical hypothyroidism (SHT) are common in clinical practice. However, the clinical significance of SHT, including prognosis, has not been established. Further clarifying SHT will be critical in devising a management plan and treatment guidelines for SHT patients. Thus, the aim of this study was to investigate the prognostic factors of SHT. METHODS: We reviewed the medical records of Korean patients who visited the endocrinology outpatient clinic of Severance Hospital from January 2008 to September 2012. Newly-diagnosed patients with SHT were selected and reviewed retrospectively. We compared two groups: the SHT maintenance group and the spontaneous improvement group. RESULTS: The SHT maintenance group and the spontaneous improvement group had initial thyroid-stimulating hormone (TSH) levels that were significantly different (P=0.035). In subanalysis for subjects with TSH levels between 5 to 10 microIU/mL, the spontaneous improvement group showed significantly lower antithyroid peroxidase antibody (anti-TPO-Ab) titer than the SHT maintenance group (P=0.039). Regarding lipid profiles, only triglyceride level, unlike total cholesterol and low density lipoprotein cholesterol, was related to TSH level, which is correlated with the severity of SHT. Diffuse thyroiditis on ultrasonography only contributed to the severity of SHT, not to the prognosis. High sensitivity C-reactive protein and urine iodine excretion, generally regarded as possible prognostic factors, did not show any significant relation with the prognosis and severity of SHT. CONCLUSION: Only initial TSH level was a definite prognostic factor of SHT. TPO-Ab titer was also a helpful prognostic factor for SHT in cases with mildly elevated TSH. Other than TSH and TPO-Ab, we were unable to validate biochemical prognostic factors in this retrospective study for Korean SHT patients.
Ambulatory Care Facilities ; C-Reactive Protein ; Cholesterol ; Cholesterol, LDL ; Endocrinology ; Humans ; Hypothyroidism* ; Iodine ; Medical Records ; Peroxidase ; Prognosis ; Retrospective Studies ; Thyroid Gland ; Thyroiditis ; Thyrotropin ; Triglycerides ; Ultrasonography

Esophageal intramural pseudodiverticulosis (EIP) is a rare benign disease that is characterized by multiple tiny flask-shaped outpouching lesions of the esophageal wall. The etiology is unknown, but the pathologic findings include dilatation of excretory ducts of submucosal glands. The predominant symptom is dysphagia, and esophageal stricture occurs frequently. Diseases such as diabetes mellitus, esophageal candidiasis, gastroesophageal reflux disease, and chronic alcoholism are often combined. Since most EIP cases are benign, the mainstream treatment is symptom relief by endoscopic dilatation or medical treatment of accompanied diseases. This report describes the case of a 68-year-old male patient who suffered from chest tightness for 2 months and was diagnosed with EIP. This symptom disappeared after 2 months of medical treatment, and the patient is now being regularly followed up.
Aged ; Alcoholism ; Candidiasis ; Deglutition Disorders ; Diabetes Mellitus ; Dilatation ; Esophageal Neoplasms ; Esophageal Stenosis ; Gastroesophageal Reflux ; Humans ; Male ; Thorax

Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself.
Acro-Osteolysis/complications/*drug therapy ; Adult ; Bone Density Conservation Agents/*therapeutic use ; Diphosphonates/*therapeutic use ; Female ; Hajdu-Cheney Syndrome/complications/*drug therapy ; Humans ; Imidazoles/*therapeutic use ; Osteoporosis/complications/*drug therapy

BACKGROUND/AIMS: Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) is rare and represents 1~2% of all pituitary adenomas. TSHoma should be distinguished from the thyroid hormone resistance syndrome. Patients with TSHoma may be misdiagnosed with primary hyperthyroidism and often receive inappropriate thyroid gland treatment. METHODS: We assessed the clinical characteristics of patients with TSHoma who presented to Severance Hospital at the Yonsei University College of Medicine, Seoul, Korea between 2005 and 2009. RESULTS: Of 484 patients who underwent pituitary tumor resection, eight (1.65%; five women and three men) were found to have TSHoma. The mean age was 40.6+/-8.9 years at diagnosis (range, 28~55 years). The median duration from onset of symptoms to diagnosis was 17 months (range, 4~60 months). Four patients had overt symptoms of hyperthyroidism and two had visual field defect. Six patients had elevated free thyroxine (FT4) levels with elevated or inappropriately normal TSH levels, and two patients had symptoms associated with Hashimoto's thyroiditis. The serum levels of free alpha-subunit measured in two patients were elevated. Six of the tumors were macroadenomas (>10 mm) and two were microadenomas. Complete tumor removal was achieved in all patients. Five patients had preoperative anterior pituitary dysfunction; three patients recovered from this after surgery. Three patients were lost to follow up and five patients showed no evidence of recurrence or hyperthyroidism in the follow-up period (mean, 30.8 months, range, 3~57). CONCLUSIONS: Early diagnosis and complete removal of the tumor mass may improve the neurological and endocrine deficits.
Early Diagnosis ; Female ; Follow-Up Studies ; Humans ; Hyperthyroidism ; Korea ; Lost to Follow-Up ; Pituitary Neoplasms ; Recurrence ; Thyroid Gland ; Thyroid Hormone Resistance Syndrome ; Thyroiditis ; Thyrotropin ; Thyroxine ; Visual Fields