Cushing's Syndrome in a Morbidly Obese Patient Undergoing Evaluation before Bariatric Surgery

Objective: Cushing's syndrome (CS) is extremely rare in morbidly obese patients. To date, no occurrences in obese patients with BMI above 60 kg/m2 have been reported in the literature. Case Report: This case report describes a patient who was admitted to the ward of the Clinical Division of Endocrinology and Metabolism of the Medical University of Vienna in preparation for bariatric surgery. The patient was a 49-year-old female who showed morbid obesity (BMI 61.6 kg/m2), hypertension, and substituted hypothyroidism. Preoperative work-up revealed CS due to an adrenal adenoma. Therefore, the patient underwent unilateral adrenalectomy followed by bariatric surgery 6 months later. Conclusion: Since undiagnosed CS might result in severe perioperative complications in a population already at increased risk, this case report underlines the importance of careful endocrine evaluation of morbidly obese patients. After all, even rare endocrine causes should be excluded

Andere spezifische Diabetesformen

Zahlreiche endokrine Erkrankungen können Störungen des Kohlenhydratstoffwechsels bewirken und zur Manifestation eines Diabetes mellitus führen bzw. diese begünstigen. Mit Ausnahme der Hyperthyreose, bei der dies nur in Ausnahmefällen zu beobachten ist, sind diese Erkrankungen selten. Akromegalie und Cushing-Syndrom sind besonders häufig mit gestörter Glukosetoleranz oder Diabetes assoziiert, bei Phäochromozytom und Conn-Syndrom stellt dies die Ausnahme dar. Bei Medikamenten, die zur Manifestation eines Diabetes führen können, sind in erster Linie Hormone, atypische Antipsychotika und Immunsuppressiva anzuführen. Weiters kommen Pankreaserkrankungen wie Pankreatitis, Pankreaskarzinom, zystische Fibrose und Hämochromatose als sekundäre Diabetesursachen in Frage, ebenso wie das Down-Syndrom, das Klinefelter-Syndrom, das Turner-Syndrom und das Prader-Willi-Syndrom sowie andere seltenere immunmediierte oder genetische Syndrome.Numerous endocrine diseases are associated with impaired glucose metabolism and can induce diabetes mellitus. With the exception of hyperthyroidism, where this is uncommon, these diseases are rare. Acromegaly and Cushing syndrome are frequently associated with impaired glucose tolerance and diabetes. In contrast, this is a rare finding in pheochromocytoma and Conn syndrome. Among the many drugs that can induce diabetes this can be observed most frequently with hormones, atypic antipsychotic drugs and immunosuppressives. In addition, diseases of the pancreas such as pancreatitis, pancreatic carcinoma, cystic fibrosis and hemochromatosis can cause diabetes as well as Down syndrome, Klinefelter syndrome, Turner syndrome and Prader Willi syndrome and rare immunmediated or genetic syndromes.(VLID)346207

Differential Regulation of Plasma Obestatin and Ghrelin by Meal Intake and the Cholinergic System in Lean, But Not Obese Individuals

Context: Obestatin is cosecreted with and stemming from the same precursor as ghrelin and is apparently involved in energy metabolism. Relatively little is known about the regulation of obestatin release. Objective: The regulation of obestatin release and obestatin-to-ghrelin ratios by meal intake and the cholinergic system were studied in lean and obese subjects. Design, Participants, and Setting: We conducted a randomized, double-blind, placebo-controlled, crossover study with 4 study days in eight obese (body mass index Ͼ30 kg/m 2 ) and eight matched lean (body mass index Ͻ25 kg/m 2 ) healthy subjects (two males and six females per group) at a University Clinical Research Unit. Interventions: Atropine (1 mg iv) was administered alone and in combination with breakfast (550 kcal) intake, or placebo (isotonic saline) alone and in combination with breakfast. Main Outcome Measures: We measured plasma obestatin and obestatin/ghrelin ratios. Results: Both obestatin and ghrelin/obestatin ratios decreased significantly from baseline by either atropine or meal intake in lean individuals, with the two effects adding up on the combined atropine/breakfast day. In contrast, there were no statistically significant differences in obese subjects, who also showed significantly greater association between ghrelin and obestatin values than their lean counterparts. Conclusions: Obestatin and ghrelin release is differentially regulated by meal intake and the cholinergic system in lean individuals. This regulation is impaired in obesity. (J Clin Endocrinol Metab 95: 0000 -0000, 2010) G hrelin, the octanoylated peptide produced mainly by the stomach and natural ligand to the GH secretagogue-receptor, is now well established as an orexigenic hormone mediating increased food intake resulting in a positive energy balance (1). Obestatin, an amidated cleavage product of the preproghrelin gene, was initially described as opposing the functions of ghrelin on appetite, resulting in decreased gastric food intake and weight gain in rodents, by binding to its cognate receptor, an (until then) orphan receptor termed g protein coupled receptor 39 (2). These results have been partially confirmed, but also called into question (see Ref. 3 and the references therein). Obestatin does bind to membranes of pancreatic cells and cell lines with high affinity and promotes survival o

Highly Potent Host-Specific Small-Molecule Inhibitor of Paramyxovirus and Pneumovirus Replication with High Resistance Barrier.

Multiple enveloped RNA viruses of the family Paramyxoviridae and Pneumoviridae, like measles virus (MeV), Nipah virus (NiV), canine distemper virus (CDV), or respiratory syncytial virus (RSV), are of high clinical relevance. Each year a huge number of lives are lost as a result of these viral infections. Worldwide, MeV infection alone is responsible for over a hundred thousand deaths each year despite available vaccine. Therefore, there is an urgent need for treatment options to counteract these viral infections. The development of antiviral drugs in general stands as a huge challenge due to the rapid emergence of viral escape mutants. Here, we disclose the discovery of a small-molecule antiviral, compound 1 (ZHAWOC9045), active against several pneumo-/paramyxoviruses, including MeV, NiV, CDV, RSV, and parainfluenza virus type 5 (PIV-5). A series of mechanistic characterizations revealed that compound 1 targets a host factor which is indispensable for viral genome replication. Drug resistance profiling against a paramyxovirus model (CDV) demonstrated no detectable adaptation despite prolonged time of investigation, thereby mitigating the rapid emergence of escape variants. Furthermore, a thorough structure-activity relationship analysis of compound 1 led to the invention of 100-times-more potent-derivatives, e.g., compound 2 (ZHAWOC21026). Collectively, we present in this study an attractive host-directed pneumoviral/paramyxoviral replication inhibitor with potential therapeutic application. IMPORTANCE Measles virus, respiratory syncytial virus, canine distemper virus, and Nipah virus are some of the clinically significant RNA viruses that threaten substantial number of lives each year. Limited to no availability of treatment options for these viral infections makes it arduous to handle the outbreaks. This highlights the major importance of developing antivirals to fight not only ongoing infections but also potential future epidemics. Most of the discovered antivirals, in clinical trials currently, are virus targeted, which consequently poses the challenge of rapid emergence of escape variants. Here, we present compound 1 (ZHAWOC9045), discovered to target viral replication in a host-dependent manner, thereby exhibiting broad-spectrum activity against several members of the family Pneumo-/Paramyxoviridae. The inability of viruses to mutate against the inhibitor mitigated the critical issue of generation of escape variants. Importantly, compound 1 was successfully optimized to a highly potent variant, compound 2 (ZHAWOC21026), with a promising profile for pharmacological intervention

Achievement of treatment goals for secondary prevention of myocardial infarction or stroke in 29,325 patients with type 2 diabetes: A German/Austrian DPV-multicenter analysis.

BACKGROUND: To analyze whether medical care is in accordance with guidelines for secondary prevention of myocardial infarction (MI), or stroke in patients with type 2 diabetes from Germany and Austria. METHODS: 29,325 patients (≥20 years of age) with type 2 diabetes and MI, or stroke, documented between 2006 and 2015 were selected from the Diabetes-Patienten-Verlaufsdokumentation database. We analyzed medication, clinical characteristics, and lifestyle factors according to national secondary prevention guidelines in patients with MI, or stroke, separately. RESULTS: HbA1C <7.5 % was achieved in 64.9 % (MI), and in 61.1 % (stroke) of patients. LDL <100 mg/dl was documented in 56.2 % (MI), and in 42.2 % (stroke). Non-smoking was reported in 92.0 % (MI), and in 93.1 % (stroke), physical activity in 9.6 % (MI), and 5.5 % (stroke). Target values of blood pressure (<130/80 mmHg in MI, 120/70-140/90 in stroke) were reached in 67.0 % (MI), and in 89.9 % (stroke). Prescription prevalence of inhibitors of platelet aggregation (IPA) was 50.7 % (MI), and 31.7 % (stroke). 57.0 % (MI), and 40.1 % (stroke) used statins, 65.1 % (MI), and 65.8 % (stroke) used any type of antihypertensives, and ACE inhibitors were prescribed in 49.7 % (MI), and 41.3 % (stroke). A body mass index (BMI) <27 kg/m(2) and the use of beta blockers were only recommended in subjects with MI. Of the patients with MI, 32.0 % had a BMI <27 kg/m(2), and 59.5 % used beta blockers. CONCLUSIONS: Achievement of treatment goals in secondary prevention of MI, or stroke in subjects with type 2 diabetes needs improvement. Target goals were met more frequently in patients with MI compared to subjects with stroke. Especially the use of IPA was very low in patients with stroke. There remains great potential to reduce the risk of repeated macrovascular events and premature death, as well as to increase patients' quality of life