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Abstract Context Cardiovascular disease is the leading cause of death in patients with Cushing syndrome. Cortisol excess and adverse metabolic profile could increase cardiac fat, which can subsequently impair cardiac structure and function. Objective We aimed to evaluate cardiac fat mass and distribution in patients with Cushing syndrome. Methods In this prospective, cross-sectional study, 23 patients with Cushing syndrome and 27 control individuals of comparable age, sex, and body mass index were investigated by cardiac magnetic resonance imaging and proton spectroscopy. Patients were explored before and after biochemical disease remission. Myocardial fat measured by the Dixon method was the main outcome measure. The intramyocardial triglyceride/water ratio measured by spectroscopy and epicardial and pericardial fat volumes were secondary outcome measures. Results No difference was found between patients and controls in intramyocardial lipid content. Epicardial fat mass was increased in patients compared to controls (30.8 g/m2 [20.4-34.8] vs 17.2 g/m2 [13.1-23.5], P < .001). Similarly, pericardial fat mass was increased in patients compared to controls (28.3 g/m2 [17.9-38.0] vs 11.4 g/m2 [7.5-19.4], P = .003). Sex, glycated hemoglobin A1c, and the presence of hypercortisolism were independent determinants of epicardial fat. Pericardial fat was associated with sex, impaired glucose homeostasis and left ventricular wall thickness. Disease remission decreased epicardial fat mass without affecting pericardial fat. Conclusion Intramyocardial fat stores are not increased in patients with Cushing syndrome, despite highly prevalent metabolic syndrome, suggesting increased cortisol-mediated lipid consumption. Cushing syndrome is associated with marked accumulation of epicardial and pericardial fat. Epicardial adiposity may exert paracrine proinflammatory effects promoting cardiomyopathy.

Early identification of subjects at high risk for diabetes is essential, and random HbA(1c) (A1C) may be more practical than fasting plasma glucose (FPG). The predictive value of A1C, in comparison to FPG, is evaluated for 6-year incident diabetes. From the French cohort study Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR), 1,383 men and 1,437 women, aged 30-65 years, were volunteers for a routine health check-up. Incident diabetes was defined by FPG >or=7.0 mmol/l or treatment by antidiabetic drugs. Multivariate logistic regression models were used to predict diabetes at 6 years. Receiver operating characteristic curves compared the predictive values of A1C and FPG. At 6 years, 30 women (2.1%) and 60 men (4.3%) had developed diabetes. Diabetes risk increased exponentially with A1C in both sexes (P < 0.001). After stratifying on FPG, A1C predicted diabetes only in subjects with impaired fasting glucose (IFG) (FPG >or=6.10 mmol/l): the odds ratio (95% CI) for a 1% increase in A1C was 7.20 (3.00-17.00). In these subjects, an A1C of 5.9% gave an optimal sensitivity of 64% and specificity of 77% to predict diabetes. A1C predicted diabetes, even though the diagnosis of diabetes was based on FPG, but it was less sensitive and specific than FPG. It could be used as a test if fasting blood sampling was not available or in association with FPG. In subjects with IFG, A1C is better than glucose to evaluate diabetes risk, and it could be used to select subjects for intensive early intervention.

Cu(I) catalyzed alkyne-azide cycloaddition reaction was employed to synthesize a series of anthracene-based human thymidylate synthase (hTS) inhibitor analogues. The triazolo-anthracene derivatives were characterized by ESI-MS/MS and a novel rearrangement reaction in ESI-MS/MS was observed. The mechanism is proposed whereby the protonated triazolo-anthracene derivative forms a carbocation, and then the carbocation electrophilically attacks an anthracene moiety resulting in formation of a rearrangement ion. Moreover, the carbocation prefers to attack the γ position rather than the α or β position of the anthracene moiety by an electrophilic substitution mechanism. Proposed rearrangement mechanism in ESI-MS/MS.

Disclosure: R.S. Braham: None. C. Droumaguet: None. M. Vitellius: None. J. Tran-van-nhieu: None. E. Béquignon: None. P. Desgranges: None. N. Limal: None. M. Mahevas: None. B. Godeau: None. IgG4 thyroiditis is an invasive fibrotic process involving the thyroid in a systemic disease. It is a rare inflammatory autoimmune disease with insidious presentation and nonspecific symptoms.We describe two unusual cases of mass forming IgG4 thyroiditis that were diagnosed recently in our department. The first case is about a 42-year-old woman who has a history of Hashimoto thyroiditis with hypothyroidism presenting with a rapid goiter growth, neck pain, dysphagia and hoarseness. A lymphoma was suspected. Ultrasonography shows heterogeneous hypoechoic lesions that may infiltrate the perithyroid muscles. Fine-needle aspiration (FNA) was suspicious of IgG4 infiltrative disease which was confirmed by microbiopsy. Only the thyroid was hypermetabolic on fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) Scan. No improvement under corticosteroid treatment and Rituximab. Surgery was planified to relieve pressure symptoms. The thyroid surgery was very difficult because of the extensive fibrosis and only a biopsy was performed, confirming the diagnosis and excluding malignancy. The second case is about a 68-year-old woman with a history of hypertension and Graves disease presented with a neck right mass that was suspected to be a paraganglioma, hypermetabolic on FDG PET scan with no other localisation. This mass was surrounding the right primitive carotid artery, associated with thrombi of the internal jugular vein. FNA and microbiopsy found a fibrotic non specific tissue. Thyroidectomy and surgical biopsy of the neck mass were performed with histopathology confirming IgG4 disease on the thyroid gland with fibrosis. There were no hypocalcemia in the two cases and no other localisation. IgG4 related mass-forming thyroiditis is an extremely rare disease. It is now a recognizable pattern of IgG4 thyroiditis, and has as differential diagnosis Hashimoto’s thyroiditis, Graves disease and thyroidal carcinoma.We will discuss through these cases the different clinical presentation of this rare disease, the diagnostic tools, the treatment and the long term follow up. Presentation: Friday, June 16, 2023

Use of HbA 1c in Predicting Progression to Diabetes in French Men and Women Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) Celine Droumaguet , MD, MSC 1 , Beverley Balkau , PHD 1 2 , Dominique Simon , MD, PHD 1 2 3 , Emile Caces , MSC 4 , Jean Tichet , MD 4 , Marie Aline Charles , MD 1 2 , Eveline Eschwege , MD 1 2 and the DESIR Study Group * 1 Institut National de la Santé et de la Recherche Médicale U258, Villejuif, France 2 Faculté de Médecine, University of Paris-Sud, Villejuif, France 3 Service de Diabétologie et Métabolisme, Groupe Hospitalier Pitié-Salpêtrière, Paris, France 4 Institut inter-Régional pour la Santé, La Riche, France Address correspondence and reprint requests to Beverley Balkau, INSERM U258-IFR69, 16 avenue Paul Vaillant-Couturier, 94807 Villejuif cedex, France. E-mail: balkau{at}vjf.inserm.fr Abstract OBJECTIVE —Early identification of subjects at high risk for diabetes is essential, and random HbA 1c (A1C) may be more practical than fasting plasma glucose (FPG). The predictive value of A1C, in comparison to FPG, is evaluated for 6-year incident diabetes. RESEARCH DESIGN AND METHODS —From the French cohort study Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR), 1,383 men and 1,437 women, aged 30–65 years, were volunteers for a routine health check-up. Incident diabetes was defined by FPG ≥7.0 mmol/l or treatment by antidiabetic drugs. Multivariate logistic regression models were used to predict diabetes at 6 years. Receiver operating characteristic curves compared the predictive values of A1C and FPG. RESULTS —At 6 years, 30 women (2.1%) and 60 men (4.3%) had developed diabetes. Diabetes risk increased exponentially with A1C in both sexes ( P < 0.001). After stratifying on FPG, A1C predicted diabetes only in subjects with impaired fasting glucose (IFG) (FPG ≥6.10 mmol/l): the odds ratio (95% CI) for a 1% increase in A1C was 7.20 (3.00–17.00). In these subjects, an A1C of 5.9% gave an optimal sensitivity of 64% and specificity of 77% to predict diabetes. CONCLUSIONS —A1C predicted diabetes, even though the diagnosis of diabetes was based on FPG, but it was less sensitive and specific than FPG. It could be used as a test if fasting blood sampling was not available or in association with FPG. In subjects with IFG, A1C is better than glucose to evaluate diabetes risk, and it could be used to select subjects for intensive early intervention. DESIR, Data from an Epidemiological Study on the Insulin Resistance Syndrome FPG, fasting plasma glucose IFG, impaired fasting glucose IGT, impaired glucose tolerance OGTT, oral glucose tolerance test ROC, receiver operating characteristic Footnotes * ↵ * A complete list of DESIR Study Group members can be found in the appendix . A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C Section 1734 solely to indicate this fact. Accepted April 13, 2006. Received December 23, 2005. DIABETES CARE

Early identification of subjects at high risk for diabetes is essential, and random HbA^sub 1c^ (A1C) maybe more practical than fasting plasma glucose (FPG). The predictive value of A1C, in comparison to FPG, is evaluated for 6-year incident diabetes. From the French cohort study Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESlR), 1,383 men and 1,437 women, aged 30-65 years, were volunteers for a routine health check-up. Incident diabetes was defined by FPG ≥7.0 mmol/1 or treatment by antidiabetic drugs. Multivariate logistic regression models were used to predict diabetes at 6 years. Receiver operating characteristic curves compared the predictive values of A1C and FPG. At 6 years, 30 women (2.1%) and 60 men (4.3%) had developed diabetes. Diabetes risk increased exponentially with A1C in both sexes (P < 0.001). After stratifying on FPG, A1C predicted diabetes only in subjects with impaired fasting glucose (IFG) (FPG ≥6.10 mmol/1): the odds ratio (95% CI) for a 1% increase in A1C was 7.20 (3.00-17.00). In these subjects, an A1C of 5.9% gave an optimal sensitivity of 64% and specificity of 77% to predict diabetes. A1C predicted diabetes, even though the diagnosis of diabetes was based on FPG, but it was less sensitive and specific than FPG. It could be used as a test if fasting blood sampling was not available or in association with FPG. In subjects with IFG, A1C is better than glucose to evaluate diabetes risk, and it could be used to select subjects for intensive early intervention.