Advanced Bone Age and Hyperinsulinemia in Overweight and Obese Children

ObjectiveIn obese children, bone age (BA) tends to significantly exceed chronological age (CA). In vitro studies in mice suggest that insulin may directly modulate skeletal growth. We investigated whether there is an association between fasting insulinand BAmaturationinobesechildren.MethodsThe study cohort comprised 74 overweight and obese children ages 4 to 13 years. BA divided by CA was used as an index for bone advancement. Participants were classified into tertiles based on their BA:CA ratio. Advanced BA maturation was defined as the third tertile, with BA:CA > 1.21. Components of the metabolic syndrome, including fasting insulin, fasting glucose, triglycerides, and high-density lipoprotein (HDL) levels, were measured.ResultsChildren with advanced BA were significantly younger, had a higher body mass index (BMI)-Z score (BMI-Z), and were taller than children with bone advancement in the lower tertiles. Females had a 4.7-fold increased risk for advanced BA compared with males (95% confidence interval [CI], 1.29-17.1; P = .02). Children with a BMI-Z ≥ 1.96 and fasting insulin ≤ 30 μU/L had a 3.6-fold increased risk of advanced BA (95% CI, 1.00-12.8; P = 0.05). Moreover, hyperinsulinemia (fasting insulin > 30 μU/L) was associated with a 6.8-fold increased risk for advanced BA, independent of the degree of obesity (95% CI, 1.45-32.1; P = .01).ConclusionMarked hyperinsulinemia is associated with advanced BA in obese children. Insulin appears to modulate skeletal growth in humans. (Endocr Pract. 2014;20:62-67)     

Differences in Bone Age Readings Between Pediatric Endocrinologists and Radiologists

Objective: Pediatric endocrinologists (PEs) have historically read their own bone age (BA) X-rays based on the belief that radiologists do not accurately interpret these tests. Whether there are significant differences in BA interpretations between these two groups has not been systematically explored. The objectives of the study were to compare BA readings performed by PEs and radiologists and determine whether clinical variables were associated with discrepancies in readings.Methods: A retrospective chart review of children presenting for initial evaluation of short stature (SS) or precocious puberty (PP) who had a BA X-ray completed was performed. Clinical variables analyzed included age, gender, ethnicity, Tanner stage, body mass index, reason for referral, radiologist location (Children's vs. outside hospital), and PE and radiologist BA readings using the Greulich and Pyle method.Results: Of 103 patients aged 9 ± 3.66 years, there was a discrepancy between the PE and radiologist readings on 70 images (68%). Discrepancy ranged from -1.5 to 3.5 years, with a mean of 4 ± 12 months. Patients referred for PP were more likely to have discrepant interpretations than those referred for SS (8.4 months vs. 0.8 months; P = .007). No differences were seen in interpretations between in-house radiologists and those at outside hospitals.Conclusion: Radiologists interpreted BAs differently than PEs in the majority of images. In patients referred for PP, BAs were interpreted as being older by radiologists than by PEs, perhaps due to bias from the reason for referral. Our results provide support for continued independent BA interpretations by PEs.Abbreviations: BA = bone age; GP = Greulich and Pyle; PE = pediatric endocrinologist; PP = precocious puberty; SS = short stature     

Efficacy and Safety of Ideglira in Older Patients with Type 2 Diabetes

Objective: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years.Methods: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1–receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V).Results: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, -1.0% &lsqb;-1.5; -0.6]_{95% confidence interval &lsqb;CI]}, -0.8% &lsqb;-1.0; -0.5]_{95% CI}, and -0.9% &lsqb;-1.3; -0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 &lsqb;0.2; 1.6]_{95% CI} &lsqb;P = .242]; 0.3 &lsqb;0.1; 0.5]_{95% CI} &lsqb;P<.001], and 11.8 &lsqb;3.3; 42.8]_{95% CI} &lsqb;P<.001] for DUAL II, V, and III, respectively).Conclusion: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall.Abbreviations: A1C = hemoglobin A1C; AE = adverse event; CI = confidence interval; Degludec = insulin degludec; EOT = end of trial; ETD = estimated treatment difference; FPG = fasting plasma glucose; GLP-1RA = glucagon-like peptide 1 receptor agonist; IDegLira = insulin degludec/liraglutide; IGlar U100 = insulin glargine 100 U/mL; SU = sulfonylurea; T2D = type 2 diabetes     

Predictors Of Biochemical Remission And Recurrence After Surgical And Radiation Treatments Of Cushing Disease: A Systematic Review And Meta-Analysis

Objective: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease.Methods: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs).Results: First-line TSS was associated with high remission (76% &lsqb;95% CI, 72 to 79%]) and low recurrence rates (10% &lsqb;95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive–adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% &lsqb;95% CI, 61 to 77%]; RT, 66% &lsqb;95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% &lsqb;95% CI, 16 to 60%]; RT, 26% &lsqb;95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence.Conclusion: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.Abbreviations:ACTH = adrenocorticotropic hormoneMRI = magnetic resonance imagingRS = radiosurgeryRT = radiotherapySC = serum cortisolTSS = transsphenoidal surgeryUFC = urinary free cortisol     

Association Between Serum Uric Acid Level and Body Mass Index in Sex- and Age-Specific Groups in Southwestern China

Objective: To investigate the sex- and age-specific association between serum uric acid level and body mass index (BMI).Methods: A total of 144,856 subjects aged 20 to 79 years were enrolled in this cross-sectional study. Serum uric acid level, renal function, hepatic function, and lipid profile were investigated.Results: The prevalence of hyperuricemia decreased with age in men but increased in women. In men, the correlation coefficient between the serum urate level and BMI declined steadily with age. Underweight was associated with a 53 to 68% and a 66% lower prevalence of hyperuricemia in men aged 20 to 69 years and in women aged 20 to 29 years, respectively. Overweight and obesity were correlated with a higher odds ratio (OR) (95% confidence interval &lsqb;CI]) for hyperuricemia in both genders. In individuals with overweight or obesity, younger subjects had a higher OR (95% CI) for hyperuricemia than older subjects. Among subjects aged 20 to 59 years, as they gained weight, the OR (95% CI) for hyperuricemia increased faster in women than in men compared with their respective normal-weight controls.Conclusion: Underweight was associated with a lower prevalence of hyperuricemia in men aged ≤69 years. In individuals with overweight or obesity, younger subjects were more likely to develop hyperuricemia than older subjects. With active weight gain, the likelihood for developing hyperuricemia increased faster in women than in men compared with their respective normal-weight controls.Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; CI = confidence interval; eGFR = estimated glomerular filtration rate; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OR = odds ratio     

High Ratio of Early Postoperative Calcitonin to Preoperative Calcitonin Could be a Novel Indicator of Poor Prognosis in Patients with Biochemical Incomplete Responses in Sporadic Medullary Thyroid Cancer

Objective: In a cohort of medullary thyroid cancer (MTC) patients with biochemical incomplete responses, 37 to 48% developed structural persistent disease; however, few indictors were available to distinguish those patients who were more likely to develop structural disease. We hypothesized that the relationship between preoperative calcitonin (Ctn) and postoperative Ctn (within 3 days after surgery) could be used to predict early prognosis of these patients.Methods: A total of 92 sporadic MTC patients were enrolled in this study. Our team proposed a novel indicator of structural persistent MTC called the calcitonin ratio (CR; CR = postoperative Ctn/preoperative Ctn). Cox regression models and the Kaplan-Meier method were used to evaluate the prognostic capability of CR. The area under the time-dependent receiver-operating characteristic curves (AUC) and the Harrell concordance index (C-index) were used for analysis.Results: The cutoff CR value used to determine MTC prognosis was 0.15. Multivariate Cox analysis revealed that CR (hazard ratio &lsqb;HR]: 22.974, 95% confidence interval &lsqb;CI]: 3.259 to 161.959, P = .002), tumor-node-metastasis (HR: 3.968, 95% CI: 1.360 to 21.857; P = .031), and multifocality (HR: 8.466, 95% CI: 1.286 to 55.716; P = .026) independently correlated with MTC prognosis. Kaplan-Meier survival curves demonstrated a lower proportion with structural persistent disease in patients with CR <0.15 (P<.001). The 3, 5, and 10-year AUC values were 0.798, 0.752, and 0.743, respectively. The C-index of CR was 0.788 (95% CI: 0.763 to 0.813).Conclusion: In this study, CR was identified as a sensitive and specific risk stratification marker for patients with biochemical incomplete responses in sporadic MTC.Abbreviations: ATA = American Thyroid Association; AUC = area under curve; CEA = carcinoembryonic antigen; CR = calcitonin ratio; Ctn = calcitonin; HR = hazard ratio; MTC = medullary thyroid cancer; ROC = receiver operating characteristic; TNM = tumor-node-metastasis     

Can Neck Circumference Predict Metabolic Syndrome? An Experience From A University Community

Objective: Neck circumference (NC) is associated with cardiovascular risk factors. The data for the measurement of the NC to predict metabolic syndrome (MetS) are limited. The objectives of this study were to determine the capability of the NC to detect MetS and to identify the optimal cutoff points of the NC among Thais.Methods: Participants who were aged ≥50 years who attended the Healthy Ageing Khon Kaen University Campus Project between March 2012 and April 2015 were recruited to this cohort study specific for atherosclerotic-related diseases. Baseline characteristics, anthropometric measures including NC, and metabolic profiles were collected. MetS was identified using the criteria of the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III) and International Diabetes Foundation (IDF).Results: There were 201 males and 386 females recruited for this study. The areas under the receiver operating characteristic (ROC) curves (AUCs) of NC based on the IDF criteria for females and males were 0.79 (95% confidence interval [CI] 0.75, 0.84) and 0.84 (95% CI 0.79, 0.9), respectively. For the NCEP ATP III criteria, the AUCs were 0.77 (95% CI 0.72, 0.82) in females and 0.71 (95% CI 0.64, 0.78) in males. An NC of 39 cm using IDF criteria for makes was determined as the optimal cutoff point to identify subjects with MetS. An NC of 33 cm for females was the best cutoff point for determining which subjects had MetS using both criteria.Conclusion: NC measurement and the use of established cutoff points is useful for predicting MetS in older Thai people.Abbreviations:AUC = area under the curveBMI = body mass indexCI = confidence intervalDM = diabetes mellitusHDL = high-density lipoproteinIDF = International Diabetes FoundationMetS = metabolic syndromeNC = neck circumferenceNCEP ATP III = National Cholesterol Educational Program Adult Treatment Panel IIIROC = receiver operating characteristicWC = waist circumference     

Prognostic Impact of Diabetes Mellitus on Overall Survival in a Nationwide Population-Based Cohort of Patients With Pancreatic Cancer

Objective: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality.Methods: This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (>2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed.Results: Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P<.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P<.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P<.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratio &lsqb;HR], 1.26; 95% confidence interval &lsqb;CI], 1.20 to 1.33; P<.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment.Conclusion: After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer.Abbreviations: CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database     

Initial Adoption of Recombinant Human Thyroid-Stimulating Hormone Following Thyroidectomy in the Medicare Thyroid Cancer Patient Population

Objective: Recombinant human thyroid-stimulating hormone (rhTSH) has been approved for diagnostic (1998) and therapeutic (2008) indications in conjunction with radioactive iodine (RAI) administration post-thyroidectomy. Potential benefits of rhTSH, including avoidance of hypothyroidism side effects and shorter, less costly hospital stays, have not been assessed at the population level within the United States. In this study we quantify utilization, outcomes, and associated costs of rhTSH within the nationally representative Surveillance, Epidemiology, and End Results (SEER)-Medicare patient population.Methods: We conducted a retrospective analysis of beneficiaries aged >65 years diagnosed within the SEER-Medicare data with differentiated thyroid cancer. Endpoints examined included (1) rhTSH utilization in the 2 years post-thyroidectomy (patients diagnosed 1996–2011 &lsqb;utilization cohort]) and (2) comparison of resource utilization and costs as a function of rhTSH receipt in the 30 days prior to and 1 year following therapeutic RAI administration (patients diagnosed 2008–2011 &lsqb;resource use cohort]). All costs were adjusted to reflect 2013 dollars.Results: A total of 6,482 patients met inclusion criteria, of which, 1,363 (21.0%) received rhTSH. Receipt varied by region and was higher in the South (18%), Northeast (28%), and West (44%) compared to the Midwest (10%), and lower in census tracts in the bottom quartile of high school education rates (odds ratio 0.68, 95% confidence interval &lsqb;CI] 0.55–0.83). rhTSH receipt was not associated with patient sex, age, comorbidities, or stage. Post-therapeutic RAI, 1,444 patients were assessed for resource utilization (2008–2011). The average cost of rhTSH was $905 per patient, with $2,483 being spent on average among patients who received rhTSH in association with therapeutic RAI. rhTSH receipt was not significantly associated with total inpatient days or number of outpatient and emergency department visits. Multivariable analyses showed similar overall costs among patients who did versus did not receive rhTSH (cost ratio &lsqb;CR] 0.96, 95% CI 0.86–1.09), partially due to increased mean outpatient costs ($5,213 vs. $4,190) being offset by lower inpatient costs ($3,493 vs. $6,143). Overall costs were significantly higher in multivariable analyses among patients with distant metastatic disease (CR 1.92, 95% CI 1.58–2.32) and multiple comorbidities (CR 2.15, 95% CI 1.83–2.53).Conclusion: rhTSH recipients had higher outpatient, lower inpatient, and similar total Medicare payments as those not receiving rhTSH in conjunction with RAI, lending support to the use of rhTSH as a cost-neutral treatment option from the payer perspective.Abbreviations: CI = confidence interval; CMS = Centers for Medicare & Medicaid Services; CR = cost ratio; HCPCS = Healthcare Common Procedure Coding System; IQR = interquartile range; mCi = millicurie; OR = odds ratio; PET = positron emission tomography; RAI = radioactive iodine; rhTSH = recombinant human thyroid-stimulating hormone; RR = risk ratio; SEER = Surveillance, Epidemiology, and End Results     

Previous Delivery of Macrosomia is Associated with Maternal Adiposity in Later Life in Chinese Parous Women with Normal Weight Before and/or After Pregnancy

Objective: Obesity has become a major worldwide health challenge. Macrosomic infants are more likely to experience type 2 diabetes mellitus, obesity and hypertension in adulthood. However, whether macrosomia increases the risk of maternal adiposity later in life is still unknown.Methods: One thousand nine hundred eighty-six unrelated parous women of Chinese Han ancestry aged from 40 to 76 years were enrolled. Self-reported information about reproductive status, including age at menarche, number of children, previous delivery of macrosomic infants, and body weight before and after pregnancy were obtained from personal interview by trained interviewers using a standard questionnaire. Macrosomia was defined as birth weight greater than 4,000 g. Adiposity indexes were measured or calculated.Results: Prior delivery of macrosomia was associated with an increased risk of having obesity in parous women with normal weight before pregnancy (odds ratio &lsqb;OR] = 1.840; 95% confidence interval &lsqb;CI] 1.028, 3.294; P = .040), as well as a higher risk of overweight/obesity in parous women with normal weight after pregnancy (OR = 1.777; 95% CI 1.131, 2.794; P = .013). In addition, previous delivery of macrosomia was related with 1.919 (95% CI 1.207, 3.050; P = .006) times higher risk of overweight/obesity in parous women with normal weight before and after pregnancy.Conclusion: The present study suggests that prior delivery of macrosomia may be an independent risk factor for adiposity later in life in parous women with normal weight before and/or after pregnancy.Abbreviations: BMI = body mass index; CI = confidence interval; OR = odds ratio; WC = waist circumference; WHR = waist-to-hip ratio; WHtR = waist-to-height ratio     

Upstroke Time Per Cardiac Cycle is Associated with Cardiovascular Prognosis in Type 2 Diabetes

Objective: Upstroke time per cardiac cycle (UTCC) in the lower extremities has been found to be predictive of cardiovascular mortality in the general population. Therefore, the purpose of the study was to test the associations between increasing UTCC and outcomes in patients with type 2 diabetes.Methods: A total of 452 patients with type 2 diabetes (age, 67.5 ± 8.6 years; male, 54%) registered in a share-care program participated in the study at an outpatient clinic in Taipei Veterans General Hospital across a mean of 5.8 years. Primary outcomes were all-cause mortality hospitalization for coronary artery disease, stroke, revascularization, amputation, and diabetic foot syndrome. Secondary end-point outcome was all-cause mortality.Results: Increment of UTCC associations with primary and secondary outcomes were undertaken prior to baseline characteristic adjustments. A UTCC of 20.1% exhibited the greatest area under curve (AUC), sensitivity, and specificity balance to predict composite events in receiver operating curves (AUC, 0.63 &lsqb;P = .001]; sensitivity, 67.7%; specificity, 54.9%). Sixty-four composite events and 17 deaths were identified from medical records. UTCC ≥20.1% was associated with the occurrence of composite events and an increased risk of mortality. For composite events, an adjusted hazard ratio (HR) of 2.45 and 95% confidence interval (CI) of 1.38 to 4.35 (P = .002) were calculated. For all-cause mortality, an adjusted HR of 1.91 and 95% CI of 0.33 to 10.99 (P = .467) were calculated.Conclusion: Increasing UTCC was associated with cardiovascular outcomes in patients with type 2 diabetes. Therefore, UTCC is advocated as a noninvasive screening tool for ambulatory patients with type 2 diabetes.Abbreviations: CAD = coronary artery disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; HR = hazard ratio; PAD = peripheral artery disease; UTCC = upstroke time per cardiac cycle     

The Effects of Perioperative Dexamethasone on Glycemic Control and Postoperative Outcomes

Objective: Perioperative glucocorticoids are commonly given to reduce pain and nausea in patients undergoing surgery. However, the glycemic effects of steroids and the potential effects on morbidity and mortality have not been systematically evaluated. This study investigated the association between perioperative dexamethasone and postoperative blood glucose, hospital length of stay (LOS), readmission rates, and 90-day survival.Methods: Data from 4,800 consecutive orthopedic surgery patients who underwent surgery between 2000 and 2016 within a single health system were analyzed retrospectively.Results: Patients with and without diabetes mellitus (DM) who were given a single dose of dexamethasone had higher rates of hyperglycemia during the first 24 hours after surgery as compared to those who did not receive dexamethasone (hazard ratio &lsqb;HR] was 1.81, and 95% confidence interval &lsqb;CI] was &lsqb;1.46, 2.24] for the DM cohort; HR 2.34, 95% CI &lsqb;1.66, 3.29] for the nonDM cohort). LOS was nearly 1 day shorter in patients who received dexamethasone (geometric mean ratio &lsqb;GMR] 0.79, 95% CI &lsqb;0.75, 0.83] for patients with DM; GMR 0.75, 95% CI &lsqb;0.72, 0.79] for patients without DM), and there was no difference in 90-day readmission rates. In patients without DM, dexamethasone was associated with a higher 90-day overall survival (99.07% versus 96.90%; P = .004).Conclusion: In patients with and without DM who undergo orthopedic surgery, perioperative dexamethasone was associated with a transiently higher risk of hyperglycemia. However, dexamethasone treatment was associated with a shorter LOS in patients with and without DM, and a higher overall 90-day survival rate in patients without DM, compared to patients who did not receive dexamethasone.Abbreviations: BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; DM = diabetes mellitus; GMR = geometric mean ratio; HR = hazard ratio; IV = intravenous; LOS = length of stay; POD = postoperative day     

Association of the vascular endothelial growth factor (VEGF-1154G>A) polymorphism in patients with colorectal cancer

Angiogenesis plays a pivotal role in the development of colon cancer during the promotion and metastasis of tumor growth. Vascular endothelial growth factor (VEGF) is known to be a potent angiogenic factor. This hospital-based case-control study was carried out to decide where there existed an association between the VEGF-1154G>A polymorphism and the susceptibility to colon cancer. DNA samples taken from 278 colon cancer patients and 226 healthy controls were studied using with real-time PCR for VEGF-1154G>A polymorphism. Genotype frequencies of the VEGF-1154G>A polymorphism were significantly different between patient and control groups (adjusted OR=2.735, 95% CI=1.243?6.015 for AA vs. GG genotype). In addition, upon stratification by gender and age, the frequencies of the A allele-bearing genotypes significantly increased the risk for development of colon cancer in men and patients younger than 55 years (in men, adjusted OR=3.375, 95% CI=1.062?10.717, and in <55 years, adjusted OR=4.908, 95% CI=1.294?18.617). Also, upon stratification of patients with proximal and distal colon cancer individually, the association only showed these significant patterns in distal colon cancer. This study provides evidence that VEGF-1154G>A polymorphism, at least in Koreans, might be associated with risks of the colon cancer, particularly in males.     

The Influence of Surgical Extent and Parafibromin Staining on The Outcome of Parathyroid Carcinoma: 20-Year Experience From a Single Institute

Objective: Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial.Methods: Clinical information and parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated.Results: A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio &lsqb;HR], 4.13; 95% confidence interval &lsqb;CI], 1.73 to 9.87; P = .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31; P = .008) was related to mortality. The extent of resection was not related to recurrence or overall survival.Conclusion: The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent.Abbreviations: CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS = overall survival; PC = parathyroid carcinoma; WHO = World Health Organization     

Risk Factors for Central Lymph Node Metastases in Patients with Papillary Thyroid Microcarcinoma

Objectives: Papillary thyroid carcinoma with a maximum tumor diameter no more than 10 mm is defined as papillary thyroid microcarcinoma (PTMC). The proportion of newly diagnosed PTMCs has increased significantly in recent years. Different guidelines have different comments about optimal management of PTMC, especially on prophylactic central lymph node (CLN) dissection. The aim of the present study was to analyze the risk factors for CLN metastases in patients with PTMC.Methods: A total of 4,389 patients underwent thyroid surgery at our center from January 2017 to March 2018, and 2,129 patients with PTMC were selected and assessed retrospectively. The relationship between CLN metastases and clinicopathologic features of PTMC were analyzed by both univariate and multivariate analyses.Results: Of the 2,129 patients with PTMC, CLN metastases were confirmed by pathology in 923 patients. Univariate and multivariate analyses found several independent factors associated with CLN metastases. They were male gender (odds ratio [OR], 1.694; 95% confidence interval [CI], 1.386 to 2.071; P<.001), younger age (<45 years) (OR, 2.687; 95% CI, 2.196 to 3.288; P<.001), larger tumor size (>5 mm) (OR, 2.168; 95% CI, 1.782 to 2.636; P<.001), positive CLN metastases via ultrasound (OR, 4.939; 95% CI, 3.534 to 6.902; P<.001), and multifocality (OR, 1.424; 95% CI, 1.176 to 1.724; P<.001).Conclusion: CLN metastases are common in PTMC patients. Male gender, younger age (<45 years), larger tumor size (>5 mm), positive CLN metastases via ultrasound, and multifocality are independent risk factors for CLN metastases. Our data should be considered in the decision-making process related to performing CLN dissection.Abbreviations: CLN = central lymph node; PTC = papillary thyroid carcinoma; PTMC = papillary thyroid microcarcinoma     

The Association of Gestational Weight Gain and Adverse Pregnancy Outcomes in Women with Gestational Diabetes Mellitus

Objective: To explore the association of excessive gestational weight gain (GWG) defined by the Institute of Medicine (IOM) targets and adverse perinatal outcomes in gestational diabetes mellitus (GDM) pregnancies, and whether a modified target might be related to a lower rate of adverse perinatal outcomes for GDM.Methods: This retrospective cohort study involved 1,138 women of normal glucose tolerance (NGT) and 1,200 women with GDM. Based on the IOM target, pregnancies were classified to appropriate GWG (aGWG), inadequate GWG, and excessive GWG (eGWG). Modified GWG targets included: upper limit of IOM target minus 1 kg (IOM-1) or 2 kg (IOM-2), both upper and lower targets minus 1 kg (IOM-1-1) or 2 kg (IOM-2-2).Results: The proportions of women achieving eGWG were 26.3% in NGT and 31.2% in GDM (P = .036); in comparison, for aGWG NGT, the risks of large for gestational age (LGA) were significantly higher in eGWG NGT (adjusted odds ratio &lsqb;OR] 1.47; 95% confidence interval &lsqb;CI] 1.02 to 2.13), aGWG GDM (adjusted OR 1.42; 95% CI 1.03 to 1.95), and eGWG GDM (adjusted OR 2.70; 95% CI 1.92 to 3.70). GDM pregnancies gaining aGWG based on the modified GWG targets (IOM-2, IOM-1-1, and IOM-2-2) had a lower prevalence of LGA and macrosomia delivery than that for similar pregnancies using the original IOM target (all P<.05).Conclusion: For aGWG GDM according to the IOM target, adhering to a more stringent weight control was associated with decreased adverse outcomes. A tighter IOM target might help to reduce the prevalence of adverse pregnancy outcomes.Abbreviations: aGWG = appropriate gestational weight gain; BG = blood glucose; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; GDM = gestational diabetes mellitus; GW = gestational weeks; GWG = gestational weight gain; HbA1c = hemoglobin A1c; iGWG = inadequate gestational weight gain; IOM = Institute of Medicine; LGA = large for gestational age; NGT = normal glucose tolerance; NICU = neonatal intensive care unit; OGTT = oral glucose tolerance test; OR = odds ratio; PARp = partial population attributable risks; SGA = small for gestational age     

Case Finding for Hypothyroidism Should Include Type 2 Diabetes and Metabolic Syndrome Patients: A Latin American Thyroid Society (LATS) Position Statement

Objective: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients.Methods: A search was made in PubMed using the following terms: “hypothyroidism” AND “diabetes” OR “metabolic syndrome.” The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected.Results: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio &lsqb;OR], 3.45; 95% confidence interval &lsqb;CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60).Conclusion: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients.Abbreviations: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Pituitary Imaging By Mri and its Correlation with Biochemical Parameters in the Evaluation of Men with Hypogonadotropic Hypogonadism

Objective: A significant ambiguity still remains about which patient deserves a magnetic resonance imaging (MRI) scan of the pituitary during evaluation of hypogonadotropic hypogonadism (HH) in men.Methods: Retrospective case series of 175 men with HH referred over 6 years.Results: A total of 49.7% of men had total testosterone (TT) levels lower than the Endocrine Society threshold of 5.2 nmol/L. One-hundred forty-two patients (81.2%) had normal appearance of pituitary MRI, whereas others had different spectrum of abnormalities (empty sella &lsqb;n = 16], macroadenoma &lsqb;n = 8], microadenoma &lsqb;n = 8], and pituitary cyst &lsqb;n = 1]). In men with TT in the lowest quartile, MRI pituitary findings were not significantly different from men in the remaining quartiles (P = .50). Patients with raised prolactin had higher number of abnormal MRI findings (38.9% vs. 13.7%; P = .0014) and adenomatous lesions (macro and micro) (27.8% vs. 4.3%; P = .01) in comparison to men with normal prolactin. The prolactin levels (median &lsqb;interquartile range]) were highest in men with macroadenomas in both groups (9,950 &lsqb;915]; P = .007 and 300 &lsqb;68.0] mU/L; P = .02, respectively), with concomitant lower levels of other pituitary hormones. Multivariate logistic regression showed an association of abnormal pituitary MRI with insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) (odds ratio &lsqb;OR], 1.78 &lsqb;95% confidence interval (CI), 1.15 to 2.77]; P = .009) and prolactin (OR, 1.00 &lsqb;95% CI, 1.00 to 1.03]; P = .01).Conclusion: MRI of the pituitary is not warranted in all patients with HH, as the yield of identifiable abnormalities is quite low. Anatomic lesions are likely to be present only when low levels of TT (<5.2 nmol/L) are found concomitantly with high levels of prolactin and/or low IGF-1 SDS.Abbreviations: CI = confidence interval; FT4 = free thyroxine; GH = growth hormone; HH = hypogonadotropic hypogonadism; IGF-1 = insulin-like growth factor; LH = luteinizing hormone; MRI = magnetic resonance imaging; OR = odds ratio; SDS = standard deviation score; TSH = thyroid-stimulating hormone; TT = total testosterone     

Validation and Comparison of Two 30-Day Re-Admission Prediction Models in Patients with Diabetes

Objective: The objective was to evaluate the 30-day re-admission predictive performance of the HOSPITAL score and Diabetes Early Re-admission Risk Indicator (DERRI™) in hospitalized diabetes patients.Methods: This was a case-control study in an academic, tertiary center in the United States. Adult hospitalized diabetes patients were randomly identified between January 1, 2014, and September 30, 2017. Patients were categorized into two groups: (1) re-admitted within 30 days, and (2) not re-admitted within 30 days. Predictive performance of the HOSPITAL and DERRI™ scores was evaluated by calculating receiver operating characteristics curves (c-statistic), Hosmer-Lemeshow goodness-of-fit tests, and Brier scores.Results: A total of 200 patients were included (100 re-admitted, 100 non–re-admitted). The HOSPITAL score had a c-statistic of 0.731 (95% confidence interval &lsqb;CI], 0.661 to 0.800), Hosmer-Lemeshow test P = .211, and Brier score 0.212. The DERRI™ score had a c-statistic of 0.796 (95% CI, 0.734 to 0.857), Hosmer-Lemeshow test P = .114, and Brier score 0.212. The difference in receiver operating characteristic curves was not statistically significant between the two scores but showed a higher c-statistic with the DERRI™ score (P = .055).Conclusion: Both HOSPITAL and DERRI™ scores showed good predictive performance in 30-day re-admission of adult hospitalized diabetes patients. There was no significant difference in discrimination and calibration between the scores.Abbreviations: CI = confidence interval; DERRI™ = Diabetes Early Re-admission Risk Indicator; IQR = interquartile range