In 2007 a question was raised about the causal relationship between the first of the glucagon-like peptide 1 receptor agonists, exenatide, and pancreatitis, as postmarketing reports of pancreatitis ...in patients treated with this agent had been received by the Food and Drug Administration (FDA). There had been six reports of hemorrhagic pancreatitis, with two of the cases resulting in death. An update of the package insert for Byetta was mandated. Sitagliptin entered the market about a year and a half later, and now there are similar reports of acute pancreatitis. As the number of patients treated with these agents increases, is it uncovering a risk not appreciated in the premarket phase or just what should be expected from the population treated with these agents? To date, 88 cases of acute pancreatitis have been reported to the FDA in patients taking sitagliptin (Januvia/Janumet). Of these, two cases have been hemorrhagic or necrotizing pancreatitis. A revision of the package insert for sitagliptin has been made recently. An examination of available data should help shed light on whether the relation is likely causal or merely incidental.
Abstract Objective The prevalence and clinical significance of incidental differentiated thyroid cancer (DTC) in patients with Graves’ disease (GD) remain uncertain. Thyroid stimulating antibody (TSI ...Ab)-titers were thought to be responsible for the potentially increased incidence or aggressiveness of PTC in that setting. The aim of this study was to compare the prevalence of incidental DTC among patients with GD and euthyroid goiter (EG), to assess the ability of TSI to predict DTC in GD and to investigate the clinical features that may predict incidental DTC in GD and EG. Methods Two hundred and forty eight patients with EG and 245 patients with GD patients who had undergone total thyroidectomy at our institution between 2005 and 2013 were retrospectively selected from our data base. An analysis of incidentally discovered DTC was conducted comparing GD group with EG group. Results Incidental micro-papillary thyroid cancer (MPTC) was found in 28% in EG group, as compared to 26% in GD group. PTC Patients with GD were significantly younger (44 vs 59) and less likely to have compressive symptoms than with EG before surgery (p < 0.001). In GD group, patients with MPTC were also significantly older (p = 0.009) than those without, were more likely to have symptomatic goiter (p < 0.001), and to have a nodular disease (p < 0.001). TSI ab titer did not predict MPTC in GD group (The AUC curve was 0.55 (95% CI: 0.46, 0.64). Among patients with GD and incidental MPTC, 58% of patients had at least one nodule. Conclusion The prevalence of incidental DTC in GD is comparable to EG. Each is increased compared to general population. Age of presentation of PTC was significantly lower in GD suggesting an increased risk for MPTC in GD. Nodule size greater than 1 cm predicted incidental DTC whereas TSI ab titers and disease duration did not.
Myocarditis, often initiated by viral infection, may progress to autoimmune inflammatory heart disease, dilated cardiomyopathy and heart failure. Although cardiac myosin is a dominant autoantigen in ...animal models of myocarditis and is released from the heart during viral myocarditis, the characterization, role and significance of anti-cardiac myosin autoantibodies is poorly defined. In our study, we define the human cardiac myosin epitopes in human myocarditis and cardiomyopathies and establish a mechanism to explain how anti-cardiac myosin autoantibodies may contribute to heart disease. We show that autoantibodies to cardiac myosin in sera from myocarditis and dilated cardiomyopathies in humans targeted primarily epitopes in the S2 hinge region of cardiac myosin. In addition, anti-cardiac myosin antibodies in sera or purified IgG from myocarditis and cardiomyopathy targeted the beta-adrenergic receptor and induced antibody-mediated cAMP-dependent protein kinase A (PKA) cell signaling activity in heart cells. Antibody-mediated PKA activity in sera was abrogated by absorption with anti-human IgG. Antibody-mediated cell signaling of PKA was blocked by antigen-specific inhibition by human cardiac myosin or the beta-adrenergic receptor but not the alpha adrenergic receptor or bovine serum albumin. Propranolol, a beta blocker and inhibitor of the beta-adrenergic receptor pathway also blocked the antibody-mediated signaling of the beta-adrenergic receptor and PKA. The data suggest that IgG antibody against human cardiac myosin reacts with the beta-adrenergic receptor and triggers PKA signaling in heart cells. In summary, we have identified a new class of crossreactive autoantibodies against human cardiac myosin and the beta-adrenergic receptor in the heart. In addition, we have defined disease specific peptide epitopes in the human cardiac myosin rod S2 region in human myocarditis and cardiomyopathy as well as a mechanistic role of autoantibody in the pathogenesis of disease.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In a 13-week, randomized trial involving persons 6 to 79 years of age with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction in the glycated hemoglobin level than ...standard care.
Abstract
Background: Ectopic production of ACTH causing Cushing’s syndrome (CS) is rare but has been well described in association with bronchial carcinoids, thymomas, pancreatic malignancies, and ...small cell lung carcinomas. We report a rare case of CS caused by ACTH-producing non-small cell carcinoma.
Clinical Case: A 71 year-old man with a history of squamous cell carcinoma of the lung (T2bN1M0) 10 years prior who underwent lobectomy and adjunctive chemotherapy, presented with a new cough, weight loss, and bilateral lower extremity edema. He was also noted to have significant fatigue, hypertension, symptomatic hyperglycemia, and hypokalemia. CT chest revealed a large right perihilar mass with mediastinal adenopathy and numerous hepatic lesions.
A biopsy of the liver lesions revealed a poorly differentiated carcinoma with neuroendocrine features strongly positive for AE1/3 with focal p40+, CK7, synaptophysin, chromogranin, and TTF1. It was negative for p63, CK5/6, CDX2, CK20, and GATA3. The morphology and immunohistochemical staining favored a squamous primary. Unfortunately, there was insufficient tissue sample to stain for ACTH. Biochemical evaluation revealed: post-1 mg dexamethasone serum cortisol 74.8 µg/dL (N < 1.8 µg/dL), 24 hr urine free cortisol 2987 µg/g creatinine (normal: < 32 µg/g creatinine), and ACTH 170 pg/mL (N < 47 pg/mL). Other notable findings at presentation were potassium 2.8 mmol/L (N: 3.7-5.1 mmol/L) and glucose 371 mg/dL (N: 74-99 mg/dL). MRI brain revealed focal pituitary infundibular thickening up to 6 mm in diameter and an enlargement of the pituitary gland concerning for metastasis. The patient’s clinical course was complicated by persistent hypokalemia and hyperglycemia which were treated with spironolactone 100 mg twice a day and insulin therapy, respectively. Ketoconazole 100 mg twice a day was initiated for the hypercortisolemia; etoposide, carboplatin, and atezolizumab were started for the neuroendocrine tumor. The patient expired due to sepsis one month after the diagnosis of Cushing’s syndrome. Conclusion: We report a rare case of paraneoplastic Cushing’s syndrome due to poorly differentiated neuroendocrine tumor with a squamous cell carcinoma primary. ACTH producing non-small cell carcinomas have been seldom reported in the literature. Although we were unable to provide ACTH staining on pathology, the existence of an obvious neuroendocrine tumor, marked elevation in ACTH, and an MRI which was negative for a pituitary adenoma, strongly suggests paraneoplastic Cushing’s syndrome.
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