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     

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     

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     

Associations Between Vitamin D and Microvascular Complications in Middle-Aged And Elderly Diabetic Patients

Objective: The objective of this cross-sectional study was to investigate the association of serum 25-hydroxyvitamin D (25&lsqb;OH]D) levels with estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and the prevalence of diabetic retinopathy (DR) in Chinese diabetic adults.Methods: A total of 4,767 diabetic participants were enrolled from seven communities in Shanghai, China, in 2018. Participants underwent several examinations, which included the measurement of anthropometric parameters, blood pressure, glucose, lipid profiles, 25(OH)D, and ACR. DR was detected based on high-quality fundus photographs and remotely read by ophthalmologists.Results: Compared with the first 25(OH)D quartile, participants in the fourth quartile had a lower prevalence of high ACR (odds ratio &lsqb;OR], 0.77; 95% confidence interval &lsqb;CI], 0.61 to 0.96) (P for trend <.01). No association was found between 25(OH)D levels and eGFR. For DR, the OR (95% CI) for DR ranging from 0 to 4 in ordinal logistic regression associated with 25(OH)D was 0.62 (0.47 to 0.82) for the fourth 25(OH)D quartile (P for trend <.01) compared with the first quartile. These associations were all fully adjusted for confounding factors.Conclusion: Lower serum 25(OH)D concentration is significantly associated with increased ACR and higher prevalence of DR in middle-aged and elderly diabetic adults. However, the possibility of a causal relationship between 25(OH)D deficiency and diabetic microvascular complications remains to be demonstrated.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; ACR = albumin/creatinine ratio; BMI = body mass index; CI = confidence interval; DKD = diabetic kidney disease; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; OR = odds ratio; T2DM = type 2 diabetes mellitus     

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     

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     

Seasonal Variation Of Vitamin D And Serum Thyrotropin Levels And Its Relationship In A Euthyroid Caucasian Population

Objective: It is unclear whether seasonal variations in vitamin D concentrations affect the hypothalamo-pituitary-thyroid axis. We investigated the seasonal variability of vitamin D and serum thyrotropin (TSH) levels and their interrelationship.Methods: Analysis of 401 patients referred with nonspecific symptoms of tiredness who had simultaneous measurements of 25-hydroxyvitamin D3 (25&lsqb;OH]D3) and thyroid function. Patients were categorized according to the season of blood sampling and their vitamin D status.Results: 25(OH)D3 levels were higher in spring-summer season compared to autumn-winter (47.9 ± 22.2 nmol/L vs. 42.8 ± 21.8 nmol/L; P = .02). Higher median (interquartile range) TSH levels were found in autumn-winter (1.9 &lsqb;1.2] mU/L vs. 1.8 &lsqb;1.1] mU/L; P = .10). Across different seasons, 25(OH)D3 levels were observed to be higher in lower quartiles of TSH, and the inverse relationship was maintained uniformly in the higher quartiles of TSH. An independent inverse relationship could be established between 25(OH)D3 levels and TSH by regression analysis across both season groups (autumn-winter: r = -0.0248; P<.00001 and spring-summer: r = -0.0209; P<.00001). We also observed that TSH varied according to 25(OH)D3 status, with higher TSH found in patients with vitamin D insufficiency or deficiency in comparison to patients who had sufficient or optimal levels across different seasons.Conclusion: Our study shows seasonal variability in 25(OH)D3 production and TSH secretion in euthyroid subjects and that an inverse relationship exists between them. Further studies are needed to see if vitamin D replacement would be beneficial in patients with borderline thyroid function abnormalities.Abbreviations: 25(OH)D2 = 25-hydroxyvitamin D2; 25(OH)D3 = 25-hydroxyvitamin D3; AITD = autoimmune thyroid disease; FT4 = free thyroxine; TFT = thyroid function test; TSH = thyrotropin; UVB = ultraviolet B     

Patients' Perception On Clinical Outcome And Quality Of Life After A Diagnosis Of Cushing Syndrome

Objective: Excess cortisol production (Cushing syndrome, CS) is a chronic disease affecting many organ systems and impacting quality of life (QoL). This study analyzed factors associated with self-reported QoL, including aspects related to the diagnosis and treatment modalities of CS.Methods: In collaboration with the Cushing's Support and Research Foundation (CSRF), surveys using a validated QoL instrument were sent to CSRF members. Data were analyzed for associations between QoL and demographic, treatment, and disease factors.Results: A total of 269 patients completed the survey. Respondents were 89.9% female, and the mean age was 48 years (SD 12, range 16–76). Respondents visited a median of 4 physicians (range 1–40) prior to the diagnosis of CS, with a median of 5 years (mean 7, SD 5, range 1–30) to obtain a diagnosis, showing a statistically significant negative correlation (P<.001). In one-quarter of cases, someone other than a physician suggested the diagnosis. Multiple regression analysis demonstrated that remission status, time to diagnosis, radiation therapy, and hypopituitarism were significant predictors of QoL. There was no association between QoL and patient's sex, age, replacement steroid use, having follow-up with an endocrinologist, or surgical approach.Conclusion: This is one of the largest QoL studies of CS patients and provides information for treatment and education goals. It is notable that early diagnosis and treatment was the major predictor of better QoL after achieving remission from disease, highlighting the need for awareness about the disorder. Patients in remission had better QoL, emphasizing the importance of disease control.Abbreviations:CD = Cushing diseaseCS = Cushing syndromeCSRF = Cushing's Support and Research FoundationQoL = quality of life     

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     

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     

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     

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     

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     

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     

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     

Outcomes of Transsphenoidal Surgery in Cushing Disease Patients with Negative Pituitary Magnetic Resonance Imaging Findings: A Single-Center Experience

Objective: Transsphenoidal surgery (TSS) is a first-line treatment for Cushing disease (CD). However, a subset of patients with CD have no visible adenoma on magnetic resonance imaging (MRI), and whether MRI results affect surgical outcomes is controversial. The aim of this study was to compare the surgical outcomes of CD patients with negative MRI findings to those of patients with positive MRI findings.Methods: The clinical features and outcomes of CD patients who underwent TSS between January 2000 and July 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinologic, histopathologic, surgical outcomes, and a minimum 12-month follow-up of 125 consecutive CD patients with negative MRI findings were compared with those of 1,031 consecutive CD patients with MRI-visible adenomas.Results: The total remission rate was 73.3% after TSS, and 11.8% of patients experienced recurrence. Of 1,031 patients with MRI-visible adenomas, postoperative remission was achieved in 762 patients (73.9%), and the recurrence of CD was observed in 94 (12.3%) patients. Of the 125 patients with negative MRI findings, postoperative remission was achieved in 85 (68%) patients, and recurrence was observed in 6 (7.1%) patients. The remission rate and recurrence rate were not significantly different between patients with negative MRI findings and those with positive MRI findings (all P>.05). The remission rate was not significantly different between patients who did or did not undergo bilateral inferior petrosal sinus sampling (BIPSS) in patients with negative MRI findings (P>.05). In the patients with negative MRI findings who underwent BIPSS, the remission rate of patients with positive BIPSS results was not different from that in patients with negative BIPSS results (P>.05). The lack of prior TSS, the detection of a tumor during operation, and pathologic confirmation of adenoma were associated with a higher surgical remission rate in patients with negative MRI findings (all P<.05). Similar results were observed in the patients with positive MRI findings (all P<.05). In addition, the major perioperative complications, including intraoperative cerebrospinal fluid leakage, hypopituitarism, and transient diabetes insipidus, were not related to the MRI results (all P>.05).Conclusion: The remission rate and recurrence rate were not different between patients with negative MRI findings and those with positive MRI findings. If CD is clearly diagnosed according to biochemical tests, radiologic examinations, and BIPSS, we recommend TSS as the first-line treatment for patients, even if the MRI results are negative.     

Causes and Predictors for 30-DAY Re-Admissions in Adult Patients with Diabetic Ketoacidosis in the United States: a Nationwide Analysis, 2010–2014

Objective: We aimed to determine the causes and predictors for 30-day re-admission following a hospitalization for diabetic ketoacidosis (DKA) in the United States.Methods: This retrospective cohort study analyzed data from the National Re-admission Database. We included adult patients with a primary discharge diagnosis of DKA, from 2010 to 2014. Our primary objective was to determine the frequency and causes for 30-day re-admission after an index hospitalization for DKA. We also performed multivariate regression analyses using covariates from the index admission to identify predictors for 30-day re-admissions.Results: Among 479,590 admissions for DKA, 58,961 (12.3%) were re-admitted within 30 days. Recurrent DKA represented 40.8% of all-cause re-admissions. In multivariate analysis, end-stage renal disease (odds ratio &lsqb;OR], 2.13; 95% confidence interval &lsqb;CI], 2.00 to 2.27; P<.001), Charlson Comorbidity Index ≥3 (OR, 2.49; 95% CI, 2.42 to 2.58; P<.001), discharge against medical advice (OR, 1.97; 95% CI, 1.86 to 2.09; P<.001), and drug use (OR, 1.78; 95% CI, 1.71 to 1.86; P<.001) were the most significant predictors for 30-day re-admission. About 50% of patients were re-admitted within 2 weeks after discharge.Conclusion: In the U.S., about one in every eight patients with DKA is re-admitted within 30 days, with 40.8% representing recurrent DKA episodes. Patients with end-stage renal disease, high comorbidity burden, drug use, and/or leaving against medical advice represented the highest risk group for re-admissions. Future studies with interventions focusing on high-risk population are critically needed.Abbreviations: AKI = acute kidney injury; BMI = body mass index; CCI = Charlson Comorbidity Index; CI = confidence interval; DKA = diabetic ketoacidosis; DM1 = type 1 diabetes mellitus; DM2 = type 2 diabetes mellitus; ESRD = end-stage renal disease; ICD-9-CM = International Classification of Diseases, Ninth Edition, Clinical Modification; IQR = interquartile range; LOS = length of stay; NRD = National Re-admission Database; OR = odds ratio     

Side Effects of PTU and MMI in the Treatment of Hyperthyroidism: A Systematic Review and Meta-Analysis

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism.Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared.Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio &lsqb;OR], 2.40; 95% confidence interval &lsqb;CI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P<.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; P = .003).Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy.Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine     

Application Of The Aace/Ace Advanced Framework For The Diagnosis Of Obesity And Cardiometabolic Disease Staging In A General Population From 3 Regions Of Venezuela: The Vemsols Study Results

Objective: To determine the prevalence of obesity according to the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) framework based on a complications-centric model with further application of the Cardiometabolic Disease Staging (CMDS) system in a Venezuelan population.Methods: A total of 1,320 adults were randomly selected from 3 regions. The AACE/ACE framework definitions were as follows: overweight, body mass index (BMI) 25 to 29.9 kg/m² and no obesity-related complications (ORC); obesity stage 0, BMI ≥30 and no ORC; stage 1, BMI ≥25 and 1 or more mild-to-moderate ORC; and stage 2, BMI ≥25 and 1 or more severe ORC. CMDS definitions were as follows: stage 0, no metabolic syndrome (MS) components; stage 1, 1 to 2 MS components without impaired fasting glucose (IFG); stage 2, IFG or ≥3 MS components but without IFG; stage 3, IFG and MS; and stage 4, type 2 diabetes (T2D) or cardiovascular disease.Results: The mean age was 44.8 ± 0.4 years, and 68.5% were female. The prevalence of obesity according to the AACE/ACE framework was 63.1%: overweight 3.0% (95% confidence interval &lsqb;CI]: 2.1–3.9); obesity stage 0: 0.1% (0.07–0.27); obesity stage 1: 26.6% (24.2–29.0); and obesity stage 2: 36.4% (33.8–39.0). Most subjects with a BMI <25 were CMDS 0 or 1. In those with BMI ≥ 25, only 4.6% were CMDS 0. The prevalence of obesity according to the World Health Organization (WHO, BMI ≥30) was 29.3% (24.7–33.7).Conclusion: In a general population study, applying the AACE/ACE framework for obesity and CMDS increased the detection of ORC and therefore higher risk subjects compared to classic anthropometric measurements.Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; BMI = body mass index; CMDS = Cardiometabolic Disease Staging; DALY = disability-adjusted life years; LA = Latin America; MS = metabolic syndrome; ORC = obesity-related complications; WC = waist circumference; WHO = World Health Organization     

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