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 [HR] was 1.81, and 95% confidence interval [CI] was [1.46, 2.24] for the DM cohort; HR 2.34, 95% CI [1.66, 3.29] for the nonDM cohort). LOS was nearly 1 day shorter in patients who received dexamethasone (geometric mean ratio [GMR] 0.79, 95% CI [0.75, 0.83] for patients with DM; GMR 0.75, 95% CI [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     

Can Microwave Ablation be an Alternative to Resection for the Treatment of Neuroendocrine Liver Metastases?

Objective: Surgical resection of neuroendocrine tumor liver metastases has been proven to improve survival, but the benefit of microwave ablation as an alternative or adjunct to surgery has yet to be assessed. Our hypothesis is that ablation is equal to surgery in terms of local recurrence and survival.Methods: We conducted a retrospective analysis including all patients treated with microwave ablation and/or surgical resection for neuroendocrine liver metastases in our institution between 2008 and 2017.Results: A total of 47 patients and 68 treatments were analyzed, including 34 liver resections, 20 ablations, and 14 combined procedures. A total of 130 individual metastases were treated with ablation, representing a median of 4 per session (range 1–30). While no major complications occurred after ablation, we observed 11 minor and 3 major complications after open surgical resection (P = .0135). Length of stay was significantly shorter after ablation (P = .0008). The majority of patients (33/47, 70.2%) underwent curative procedures, 14 patients underwent (29.8%) debulking procedures. There was no difference in local recurrence rate between tumors treated with ablation or resection. Liver-only disease progression was detected in 29% of the patients and overall progression was detected in 66% of the patients. The mean survival was not significantly different between patients treated with ablation only versus resection with or without ablation (P = .1570). Overall survival was mean 75.3 months (6 to 374 months).Conclusion: Depending on the extent of the liver metastases, microwave ablation might be a safe alternative or addition to resection for neuroendocrine tumor liver metastases with low morbidity and high local efficiency.Abbreviations: CT = computed tomography; MWA = microwave ablation; NET = neuroendocrine tumor; PET = positron emission tomography; RFA = radiofrequency ablation; RFS = recurrence-free survival; SMWA = stereotactic microwave ablation     

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% [95% CI, 72 to 79%]) and low recurrence rates (10% [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% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [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     

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     

Risk of Malignancy in Thyroid Cytology: The Impact of The Reclassification of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)

Objective: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We aimed to compare the risk of malignancy (ROM) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) on fine-needle aspiration cytology (FNAC), before and after the reclassification, in a large cohort of patients.Methods: We analyzed 5,625 consecutive FNAC samples performed in 2012–2014 and selected category III (atypia of undetermined significance &lsqb;AUS]/follicular lesion of undetermined significance &lsqb;FLUS]), IV (follicular neoplasm &lsqb;FN]/suspicious for a follicular neoplasm &lsqb;SFN]), V (suspicious for malignancy &lsqb;SFM]), and VI (malignant) of the BSRTC. We reviewed the histology of operated patients and compared ROM before and after the introduction of the NIFTP category.Results: A total of 772 patients were identified and 45% underwent surgery (n = 348). There were 180 cases of AUS/FLUS (10 NIFTP), 114 cases of FN/SFN (2 NIFTP), 29 cases of SFM (3 NIFTP), and 25 cases of BSRTC VI (no NIFTP). Exclusion of NIFTP from malignant lesions resulted in a relative and absolute decrease in the ROM in AUS/FLUS (15.2% and 5.5%, respectively), FN/SFN (7.6% and 1.8%, respectively) and SFM (14.2% and 10.3%, respectively) categories. Among the NIFTP patients, 93% underwent total thyroidectomy and 20% received radioiodine.Conclusion: Reclassification of noninvasive EFVPTC as NIFTP resulted in a decrease in overall ROM, and the BSRTC categories most affected were III and V.Abbreviations: AUS = atypia of undetermined significance; BSRTC = Bethesda System for Reporting Thyroid Cytopathology; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; FNAC = fine-needle aspiration cytology; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma; ROM = risk of malignancy; SFM = suspicious for malignancy; SFN = suspicious for a follicular neoplasm     

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     

Greater Low-Density Lipoprotein Cholesterol Variability Increases the Risk of Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

Objective: Variability in lipid levels has been associated with poor cardiovascular outcomes in patients with coronary artery disease. The aim of this study was to investigate whether low-density lipoprotein cholesterol (LDLC) variability can be used to predict cardiovascular events in patients with type 2 diabetes mellitus (DM).Methods: A total of 5,354 patients with type 2 DM were enrolled in this study. Cardiovascular events including peripheral arterial disease, coronary artery disease, stroke, and cardiovascular death were defined as the study endpoints, and standard deviations of lipid levels were used to define intra-individual lipid variability.Results: Univariate Cox proportional hazards analysis showed that LDL-C standard deviation (hazard ratio &lsqb;HR] = 1.016; 95% confidence interval &lsqb;CI] = 1.006 to 1.022; P<.001) was associated with a higher risk of cardiovascular events. Multivariate Cox proportional hazards analysis showed that an increase in LDL-C standard deviation significantly increased the risk of cardiovascular events (HR = 1.063; 95% CI = 1.025 to 1.102; P = .01). Kaplan-Meier analysis of cardiovascular event-free survival showed that the patients in tertiles 2 and 3 of the standard deviation of LDL-C had worse cardiovascular event-free survival compared to those in tertile 1.Conclusion: Variability in LDL-C could predict cardiovascular events in the patients with type 2 DM in this study.Abbreviations: CAD = coronary artery disease; CI = confidence interval; CVD = cardiovascular disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; HbA1c = glycosylated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; KMUHRD = Kaohsiung Medical University Hospital Research Database; LDL-C = low-density lipoprotein cholesterol; SD = standard deviation; UACR = urine albumin to creatinine ratio     

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     

Does T Stage Affect Prognosis in Patients With Stage Iv B Differentiated Thyroid Cancer

Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8^th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T &lsqb;primary tumor size], N &lsqb;regional lymph nodes], M &lsqb;distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival.Methods: DTC cases that were considered stage IV B in the AJCC 8^th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6^th standard) was categorized into T0–2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis.Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS.Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary.Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database     

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     

Hba1C Control And Cost-Effectiveness in Patients With Type 2 Diabetes Mellitus Initiated On Canagliflozin or A Glucagon-Like Peptide 1 Receptor Agonist in A Real-World Setting

Objective: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting.Methods: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012–April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics. HbA1c levels at 3-month intervals were compared using generalized estimating equations. Medication costs used wholesale acquisition costs.Results: For both cohorts (CANA: n = 11,435; GLP-1 RA: n = 11,582), HbA1c levels decreased at 3 months postindex and remained lower through 30 months. Absolute changes in mean HbA1c from index to 3 months postindex for CANA and GLP-1 RA were -1.16% and -1.21% (patients with baseline HbA1c ≥7% &lsqb;53 mmol/mol]); -1.54% and -1.51% (patients with baseline HbA1c ≥8% &lsqb;64 mmol/mol]); and -2.13% and -1.99% (patients with baseline HbA1c ≥9% &lsqb;75 mmol/mol]), respectively. Postindex, CANA patients with baseline HbA1c ≥7% had similar HbA1c levels at each interval versus GLP-1 RA patients, except 9 months (mean HbA1c, 7.75% &lsqb;61 mmol/mol] vs. 7.86% &lsqb;62 mmol/mol]; P = .0305). CANA patients with baseline HbA1c ≥8% and ≥9% had consistently lower HbA1c numerically versus GLP-1 RA patients and statistically lower HbA1c at 9 (baseline HbA1c ≥8% or ≥9%), 27, and 30 months (baseline HbA1c ≥9%). Continuous 12-month medication cost $3,326 less for CANA versus GLP-1 RA.Conclusion: This retrospective study demonstrated a similar evolution of HbA1c levels among CANA and GLP-1 RA patients in a real-world setting. Lower medication costs suggest CANA is economically dominant over GLP-1 RA (similar effectiveness, lower cost).Abbreviations:AHA = antihyperglycemic agentBMI = body mass indexCANA = canagliflozin 300 mgDCSI = diabetes complications severity indexeGFR = estimated glomerular filtration rateEMR = electronic medical recordGLP-1 RA = glucagon-like peptide 1 receptor agonistHbA1c = glycated hemoglobinICD-9-CM = International Classification of Diseases–Ninth Revision–Clinical ModificationICD-10-CM = International Classification of Diseases–Tenth Revision–Clinical ModificationIPTW = inverse probability of treatment weightingITT = intent-to-treatMPR = medication possession ratioPDC = proportion of days coveredPS = propensity scorePSM = propensity score matchingQuan-CCI = Quan-Charlson comorbidity indexSGLT2 = sodium-glucose cotransporter 2T2DM = type 2 diabetes mellitusWAC = wholesale acquisition cost     

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Objective: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC.Methods: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed.Results: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98–1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75–1.58, P = .662).Conclusion: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC.Abbreviations:CI = confidence intervalCLNM = cervical lymph node metastasisFVPTC = follicular variant papillary thyroid carcinomaHR = hazard ratioKM = Kaplan-MeierNCDB = National Cancer Data BaseOS = overall survivalPTC = papillary thyroid carcinomaRAI = radioactive iodine     

Bone Mineral Density In Patients With Addison Disease On Replacement Therapy With Prednisolone

Objective: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement.Methods: Forty-one consecutive patients (31 males, age &lsqb;mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent &lsqb;HCE] 13.0 ± 3.0 mg/m²) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677).Results: Among males, BMD Z-scores (mean &lsqb;95% confidence interval {CI}]) at lumbar spine (-0.42 &lsqb;-0.80, -0.04]), femoral neck (-0.50 &lsqb;-0.95, -0.06]) and total hip (-0.58 &lsqb;-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD.Conclusions: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.Abbreviations:ACTH = adrenocorticotropic hormoneBAP = bone-specific alkaline phosphataseBMD = bone mineral densityBMI = body mass indexCI = confidence intervalHCE = hydrocortisone equivalent25 (OH) D3 = 25-hydroxyvitamin D3PAI = primary adrenal insufficiency     

Can the American Thyroid Association,K-Tirads,and Acr-Tirads Ultrasound Classification Systems Be Used to Predict Malignancy in Bethesda Category IV Nodules?

Objective: Management of thyroid nodules with Bethesda category III and IV cytology on fine needle aspiration (FNA) is challenging as they cannot be adequately classified as benign or malignant. Ultrasound (US) patterns have demonstrated the utility in evaluating the risk of malignancy (ROM) of Bethesda category III nodules. This study aims to evaluate the value of 3 well-established US grading systems (American Thyroid Association &lsqb;ATA], Korean Thyroid Imaging Reporting and Data System &lsqb;Korean-TIRADS], and The American College of Radiology Thyroid Imaging Reporting and Data System &lsqb;ACR-TIRADS]) in determining ROM in Bethesda category IV nodules.Methods: Ninety-two patients with 92 surgically resected thyroid nodules who had Bethesda category IV cytology on FNA were identified. Nodule images were retrospectively graded using the 3 systems in a blinded manner. Associations between US risk category and malignant pathology for each system were analyzed.Results: Of the 92 nodules, 56 (61%) were benign and 36 (39%) were malignant. Forty-seven per cent of ATA high risk nodules, 53% of K-TIRADS category 5 nodules, and 50% of ACR-TIRADS category 5 nodules were malignant. The ATA high-risk category had 25% sensitivity, 82% specificity, 47% positive predictive value (PPV) for malignancy. K-TIRADS category 5 had 25% sensitivity, 85% specificity, 53% PPV for malignancy. ACR-TIRADS category 5 had 25% sensitivity, 84% specificity, 50% PPV for malignancy. None of the 3 grading systems yielded a statistically significant correlation between US risk category and the ROM (P = .30, .72, .28).Conclusion: The ATA, Korean-TIRADS, and ACR-TIRADS classification systems are not helpful in stratifying ROM in patients with Bethesda category IV nodules. Clinicians should be cautious of using ultra-sound alone when deciding between therapeutic options for patients with Bethesda category IV thyroid nodules.     

No Benefit of Dedicated Thyroid Nodule Screening in Patients with Acromegaly

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.).Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology.Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 &lsqb;SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 &lsqb;SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed).Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States     

Delayed 131-I First Treatment After Surgery has No Impact on the Median Term Outcome of Patients with Intermediate Risk Differentiated Thyroid Cancer

Objective: In intermediate risk (IR) differentiated thyroid cancer (DTC) patients, selective use of radioiodine (131-I) for remnant ablation and/or as adjuvant therapy (RRA) is advocated. The recently suggested postoperative evaluation could delay the use of RRA. The aim of this study was to evaluate if a delayed RRA can worsen the clinical outcome of IR-DTC patients.Methods: Four hundred and fourteen consecutive IR-DTC patients were divided according to the time elapsed from surgery to RRA, <6 months (group A, 186/414 &lsqb;44.9%]), or ≥6 months (group B, 228/414 &lsqb;55.1%]). Clinical and biochemical data were collected, and clinical outcome was analyzed at the first evaluation (EV) after RRA (first-EV) and after a median of 6 years of follow-up (last-EV).Results: No difference in the clinical outcome of group A and B was found. Since a different activity of 131-I could have an impact on the outcome, we separately analyzed the groups according to the 131-I activity (low-activity group: 1,110 MBq/30 mCi &lsqb;n = 320], and high-activity group: 3,700 MBq/100 mCi &lsqb;n = 94]), further subdivided according to the time elapsed from surgery to RRA. No major differences were found in both the low- and high-activity groups when comparing the features of their subgroups A and B, as far as in their clinical outcome.Conclusion: The time elapsed between surgery and the first 131-I treatment does not influence the clinical outcome of IR-DTC patients. This finding allows a more relaxed attitude in the decision making process whether to perform the RRA in IR-DTC cases in which a selective use of 131-I is recommended.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; EV = evaluation; HR = high risk; 131-I = radioiodine; IR = intermediate risk; LR = low risk; rhTSH = recombinant human thyroid-stimulating hormone; RRA = radioiodine for remnant ablation; Tg = thyroglobulin; TgAb = thyroglobulin autoantibody; US = ultrasound     

Total Body Adiposity,Triglycerides, and Leg Fat are Independent Risk Factors for Diabetic Peripheral Neuropathy in Chinese Patients with type 2 Diabetes Mellitus

Objective: To evaluate the risk factors associated with diabetic peripheral neuropathy (DPN) in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: Between January 2014 and December 2017, 107 participants who had obesity with T2DM and 349 participants who had normal weight with T2DM, matched for age, sex, and duration of diabetes, were recruited. The clinical and biochemical parameters were measured in each patient. DPN was diagnosed based on neuropathy symptom score and neuropathy deficit score. Motor and sensory nerve conduction velocities were measured by electromyography. Body fat mass was estimated by dual-energy X-ray absorptiometry, while hepatic steatosis was evaluated by ultrasonography.Results: The group with obesity had a significant higher prevalence of DPN (66.62%) than that (46.99%) of the group with normal weight. Compared to the patients with normal weight, the sural sensory nerve in the right lower limbs of the patients with obesity was more susceptible to damage. Hypertriglyceridemia in the patients with obesity was a significant independent risk factor for DPN (odds ratio &lsqb;OR], 3.90 &lsqb;95% confidence interval (CI), 1.01 to 15.02]; P = .04), while the duration of diabetes (OR, 1.33 &lsqb;95% CI, 1.07 to 1.65]; P<.01) and leg subcutaneous fat mass (OR, 0.72 &lsqb;95% CI, 0.57 to 0.90]; P<.01) in the patients with normal weight were independent risk factors for DPN. The presence of obesity alone in patients with T2DM could predict high DPN risk (OR, 3.09 &lsqb;95% CI, 1.11 to 8.65]; P = .04).Conclusion: Reducing total body adiposity and triglyceride levels, as well as avoiding leg subcutaneous fat atrophy, could be new prevention strategies for DPN in Chinese patients with T2DM.Abbreviations: ALB = albumin; ALT = alanine transaminase; AST = aspartate transaminase; AUC = area under the curve; AUCc-p/AUCglu = AUC of C-peptide/AUC of glucose; BMI = body mass index; BP = blood pressure; CI = confidence interval; Cr = creatinine; DBP = diastolic blood pressure; DPN = diabetic peripheral neuropathy; FC-P = fasting C-peptide; FPG = fasting plasma glucose; FFA = free fatty acid; γ-GGT = γ-glutamyl transferase; HbA1c = glycated hemoglobin A1c; HDL-C = high-density-lipoprotein cholesterol; ISI = insulin sensitivity index; ISSI-2 = insulin secretion-sensitivity index-2; LDL-C = low-density-lipoprotein cholesterol; MNCS = motor nerve conduction velocity; OGTT = oral glucose tolerance test; PG = plasma glucose; SAT = subcutaneous adipose tissue; SBP = systolic blood pressure; SNCS = sensory nerve conduction velocity; T2DM = type 2 diabetes mellitus; TC = total cholesterol; TG = triglyceride; UA = uric acid; VAT = visceral adipose tissue; WC = waist circumference     

Clinical Presentation and Outcomes of Opioid-Induced Adrenal Insufficiency

Objective: Opioid-induced adrenal insufficiency (OIAI) may develop in patients treated with chronic opioids due to suppression of the hypothalamic-pituitary-adrenal axis. Our objective was to describe the clinical manifestations, biochemical presentation, and clinical course of OIAI.Methods: A retrospective study of adults diagnosed with OIAI between 2006 and 2018 at an academic center. Opioid daily dose was converted into morphine milligram equivalents (MMEs).Results: Forty patients (women, n = 29 &lsqb;73%]) taking chronic opioids at a daily median MME dose of 105 (60 to 200) mg and median duration of 60 (3 to 360) months were diagnosed with OIAI. Patients reported fatigue (n = 29, 73%), musculoskeletal pain (n = 21, 53%), and weight loss (n = 17, 53%) for a median of 12 (range, 1 to 132) months prior to diagnosis, and only 7.5% (n = 3) of patients were identified with OIAI through case detection. Biochemical diagnosis of OIAI was based on (1) low morning cortisol, baseline adrenocorticotropic hormone and/or dehydroepiandrosterone sulfate in 59% (n = 26) of patients or (2) abnormal cosyntropin stimulation test in 41% (n = 14) of patients. With glucocorticoid replacement, 16/23 (70%) patients with available follow-up experienced improvement in symptoms. Opioids were tapered or discontinued in 15 patients, of whom 10 were followed for adrenal function and of which 7 (70%) recovered from OIAI.Conclusion: Minimum daily MME in patients diagnosed with OIAI was 60 mg. OIAI causes significant morbidity, and recognition requires a high level of clinical suspicion. Appropriate glucocorticoid treatment led to improvement of symptoms in 70%. Resolution of OIAI occurred following opioid cessation or reduction.     

Dysregulation Of The Hypothalamic-Pituitary-Adrenal Axis Increases Central Body Fat Accumulation In Males Affected By Diabetes Mellitus And Late-Onset Hypogonadism

Objective: Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH).Methods: Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered.Results: The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 &lsqb;interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 &lsqb;interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 &lsqb;P<.001]; β = 1.156 &lsqb;P<.001]; β = -7.675 &lsqb;P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH.Conclusion: Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation.Abbreviations:ACTH = adrenocorticotropic hormoneAUC = area under the curveCRH = corticotropin-releasing hormoneCT = computed tomographyDEXA = dual-energy X-ray absorptiometryDM = diabetes mellitusFH = functional hypercortisolismFH-LOH = subjects affected by functional hypercortisolismFSH = follicle-stimulating hormoneHPA = hypothalamic-pituitary-adrenalLH = luteinizing hormoneLOH = late-onset hypogonadismN-LOH = subjects not affected by functional hypercortisolismOST = overnight low-dose dexamethasone suppression testSHBG = sex hormone–binding globulinUFC = urinary free cortisol     

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