Citations

AbstractObjectivesLong-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA).MethodsHistologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated.ResultsFollow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM).ConclusionsAppropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

The characteristics of pulsatile insulin secretion are important determinants of type 2 diabetes pathophysiology, but they are understudied due to the difficulties in measuring pulsatile insulin secretion noninvasively. Deconvolution of either peripheral C-peptide or insulin concentrations offers an appealing alternative to hepatic vein catheterization. However, to do so, there are a series of methodological challenges to overcome. C-peptide has a relatively long half-life and accumulates in the circulation. On the other hand, peripheral insulin concentrations reflect relatively fast clearance and hepatic extraction as it leaves the portal circulation to enter the systemic circulation. We propose a method based on nonparametric stochastic deconvolution of C-peptide concentrations, using individually determined C-peptide kinetics, to overcome these limitations. The use of C-peptide (instead of insulin) concentrations allows estimation of portal (and not post-hepatic) insulin pulses, whereas nonparametric stochastic deconvolution allows evaluation of pulsatile signals without any a priori assumptions of pulse shape and occurrence. The only assumption required is the degree of smoothness of the (unknown) secretion rate. We tested this method first on simulated data and then on 29 nondiabetic subjects studied during euglycemia and hyperglycemia and compared our estimates with the profiles obtained from hepatic vein insulin concentrations. This method produced satisfactory results both in the ability to fit the data and in providing reliable estimates of pulsatile secretion, in agreement with hepatic vein measurements. In conclusion, the proposed method enables reliable and noninvasive measurement of pulsatile insulin secretion. Future studies will be needed to validate this method in people with type 2 diabetes.

Abstract BACKGROUND Previously defined thresholds for total testosterone (TT) concentrations to screen for androgen-producing tumors (APTs) have used RIA, which can be less accurate in women. We aimed to define diagnostic thresholds to screen for APTs or postmenopausal pathologic hyperandrogenism using TT concentrations measured by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). METHODS We performed a retrospective cohort study on all women with TT ≥3.5 nmol/L and all postmenopausal women presenting with hyperandrogenism between 2004 and 2014 at the Mayo Clinic in Rochester, MN. RESULTS Of the 369 women with TT ≥3.5 nmol/L, 89 were included and subdivided into 3 groups based on their clinical diagnosis [21 (24%), APT; 16 (18%), postmenopausal pathologic hyperandrogenism; 52 (58%), polycystic ovary syndrome]. The source of the APT was more frequently ovarian (81%, n = 17) than adrenal (19%, n = 4). The diagnostic threshold using ROC analysis for TT to identify APT in women with severe biochemical hyperandrogenemia was ≥5.1 nmol/L (sensitivity, 90%; specificity, 81%). In a second analysis of a cohort of postmenopausal women only presenting with symptoms or signs of hyperandrogenism, median TT was significantly higher in the postmenopausal pathologic hyperandrogenism group (APT and ovarian hyperthecosis) vs the idiopathic hyperandrogenism group (4.9 vs 0.8 nmol/L; P < 0.01). In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was TT ≥2.2 nmol/L (sensitivity, 100%; specificity, 86%). CONCLUSIONS The diagnostic threshold for TT concentration as measured by LC-MS/MS to identify APT in women with biochemical severe hyperandrogenemia was TT ≥5.1 nmol/L. In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was lower (TT ≥2.2 nmol/L).

Abstract Context Abnormal glucagon concentrations contribute to hyperglycemia, but the mechanisms of α-cell dysfunction in prediabetes are unclear. Objective We sought to determine the relative contributions of insulin secretion and action to α-cell dysfunction in nondiabetic participants across the spectrum of glucose tolerance. Design This was a cross-sectional study. A subset of participants (n = 120) was studied in the presence and absence of free fatty acid (FFA) elevation, achieved by infusion of Intralipid (Baxter Healthcare, Deerfield, IL) plus heparin, to cause insulin resistance. Setting An inpatient clinical research unit at an academic medical center. Participants A total of 310 nondiabetic persons participated in this study. Interventions Participants underwent a seven-sample oral glucose tolerance test. Subsequently, 120 participants were studied on two occasions. On one day, infusion of Intralipid plus heparin raised FFA. On the other day, participants received glycerol as a control. Main Outcome Measure(s) We examined the relationship of glucagon concentration with indices of insulin action after adjusting for the effects of age, sex, and weight. Subsequently, we sought to determine whether an acute decrease in insulin action, produced by FFA elevation, altered glucagon concentrations in nondiabetic participants. Results Fasting glucagon concentrations correlated positively with fasting insulin and C-peptide concentrations and inversely with insulin action. Fasting glucagon was not associated with any index of β-cell function in response to an oral challenge. As expected, FFA elevation decreased insulin action and also raised glucagon concentrations. Conclusions In nondiabetic participants, glucagon secretion was altered by changes in insulin action.

Background: Glucose variability (GV) has been increasingly (or more extensively) studied in patients with type 1 diabetes (T1D) in the ambulatory setting; limited data exist on GV in hospitalized patients with T1D. Materials and Methods: Retrospective single center cohort study, we analyzed in-hospital glucose measurements to assess GV in 736 hospitalized patients in different units over a consecutive 5-year period of time. GV was assessed by mean blood glucose (BG), Average daily risk range (ADRR), high BG index, and low BG index. To place our findings in context, we conducted a systematic review using Cochrane collaboration methodology to critically analyze current published literature on GV in hospitalized T1D patients. Results: Overall, glycemic control was suboptimal with mean BG 183 ± 51.5 mg/dL and mean ADRR 35 with only 16% patients being categorized as low risk (ADRR <20) for hypo or hyperglycemia. Patients admitted in medical units had mean BG of 194.4 ± 42.8 mg/dL (95% CI = 101.2–346.6) and ADRR of 39.4 ± 16 (95% CI = 1.3–118.7), which were higher than the patients admitted in the surgical units (mean BG 168.1 ± 35.7 (95% CI = 74.8–301.8) and mean ADRR (28.8 ± 13.1 [95% CI = 0.3–93.1]). For the systematic review, initial search yielded 2336 studies for screening, however, none of them had data specific for T1D. Conclusion: GV is high in hospitalized T1D patients admitted at our tertiary care center. Review of the literature shows paucity of data regarding GV in hospitalized patients with T1D.