1,720,971 research outputs found

    Primary symptomatic adrenal insufficiency induced by megestrol acetate

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    Megestrol acetate (MA) is a progestational agent for the treatment of metastatic breast cancer and endometrial cancer. MA has also been used to promote weight gain in malnourished elderly patients, in patients with immunodeficiency virus and in cancer-induced cachexia. In addition to thromboembolic disease, MA may induce hyperglycaemia, osteoporosis, suppression of the gonadal axis, and Cushing's syndrome. MA has also been shown to cause symptomatic suppression of the hypothalamic-pituitary-adrenal (HPA) axis owing to its intrinsic glucocorticoid-like effect. Three additional patients are presented who developed symptomatic adrenal insufficiency while they were receiving 160-320 mg MA daily. The patients were treated with cortisone acetate supplements, had clear evidence of HPA-axis suppression but recovered fully after MA was discontinued. Patients receiving MA might have an inadequate adrenal response during stressful conditions, possibly because 160-320 mg MA daily may not provide adequate protection to prevent the symptoms of adrenal insufficiency. The adverse MA effect on the HPA axis is probably not well recognised in clinical practice, and clinicians need an increased awareness of the endocrine complications secondary to MA treatment. © Van Zuiden Communications B.V. All rights reserved

    Activation of α1-adrenoceptors inhibits growth hormone secretion in humans

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    In order to determine whether an α1-adrenergic mechanism is involved in the secretion of Growth Hormone (GH) in humans, we studied the effect of the α1-adrenergic-stimulating agent methoxamine on serum GH levels in twelve normal males (age range 22-32 years). Intravenous infusion of methoxamine (dose: 6 μg/kg/min; duration: 150 min) significantly reduced serum GH levels at time 120 and 150, and on integrated concentrations. These data suggest that α1-adrenergic receptors inhibit tonic GH secretion in humans

    Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

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    Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients

    Cerebral amyloid angiopathy and atrial fibrillation: a dangerous combination

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    Intracranial hemorrhage (ICH) is the major complication of oral anticoagulant therapy. Cerebral amyloid angiopathy (CAA) is an age-related disease characterized by the pathological deposition of beta-amyloid protein in leptomeningeal and cortical cerebral vessels. Such vascular alterations expose to the risk of spontaneous vascular rupture. The main clinical manifestations are represented by ICH, cognitive decline and transient focal neurological episodes (TFNE). In the patient subgroup with TFNE, a misdiagnosis with transient ischemic attack may have catastrophic consequences, resulting in a significant increase in the risk of spontaneous ICH within weeks after clinical onset, with potentially devastating consequences if anticoagulant therapy is started.The prevention of bleeding complications related to CAA is based on disease knowledge. This is particularly relevant because non-pharmacological treatment options, including percutaneous left atrial appendage occlusion, are emerging as an alternative to traditional anticoagulant therapies in patients at high bleeding risk

    Prevalence of unknown thyroid disorders in a Sardinian cohort

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    Objective: To assess thyroid function, the presence of thyroid antibodies, as well as the presence of goiter and/or nodules in subjects without a prior diagnosis of thyroid disorders, in a region with mild to moderate iodine deficiency. Design and methods: This cross-sectional study is based on data obtained from first and third visits of participants in the Sardinian survey. We performed two different analyses. In one, we assessed the prevalence of unknown thyroid dysfunctions among 6252 subjects who had a medical examination and blood collection for assays of thyrotropin, free thyroxine, and antibodies against thyroperoxidase (AbTPO) and against thyroglobulin (AbTG). In a second analysis, we evaluated the frequency of undiagnosed goiter and nodules among 3377 subjects who had a thyroid ultrasound scan. Subjects were excluded if they had a previous history of thyroid disorders or presence of goiter and/or nodules, or thyroid surgery, or if they were taking drugs that could impair thyroid function. Results: We found a low prevalence of overt thyroid dysfunction (hyperthyroidism 0.4% and hypothyroidism 0.7%). The rates of subclinical hypothyroidism and hyperthyroidism were 4.7 and 2.4% respectively. Almost 16% of participants were positive for at least one antibody and 5.2% for both AbTG and AbTPO. Nodules were detected in 17.4% of subjects and the prevalence of goiter was 22.1%. Conclusions: Undiagnosed biochemical thyroid dysfunctions, unknown nodules, and goiter were common in subjects living in a mild to moderate iodine-deficient area. In this community, thyroid disorders often go undetected and screening could be reasonable in subjects at a higher risk

    Phenotypic heterogeneity of latent autoimmune diabetes in adults identified by body composition analysis

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    Background: In patients with Latent Autoimmune Diabetes in Adults (LADA) a lower body mass index was reported compared with classical type 2 diabetes (T2D), and was found to be associated with a faster progression to insulin-dependence. In this study we determined the body composition in a cohort of LADA patients from Sardinia, Italy, and compared it with age–and gender–matched patients diagnosed as having adult-onset type 1 diabetes (T1D) and non-autoimmune T2D. Methods: In 210 LADA patients, 210 T2D patients and 30 adult-onset T1D patients of Sardinian origin we assessed total and segmental body composition (weight-adjusted percent fat mass and lean mass) by using Dual Energy X-rays Absorptiometry (DXA). Results: In the whole cohort of LADA patients total fat mass was significantly smaller compared with T2D patients (p < 0.0001), while no difference was found between LADA and T1D patients. In LADA men fat depletion involved all body segments, while in LADA women it was observed only in the truncal segment (p < 0.0001), as in the upper and lower regions fat deposits were larger compared to T2D (p < 0.0001). However, LADA women showed a significantly elevated truncal fat compared to T1D women (p < 0.004), whereas no difference was detected in the extremities. Conclusions: Body composition in LADA patients shows substantial difference, in a gender-dependent way, compared to classic T2D. In women fat deposits tend to accumulate in peripheral regions rather than centrally, whereas in men the distribution is more homogeneous. In addition, central fat depletion in LADA women appears to be a significant predictor of faster progression to insulin dependence. Thus, routine assessment of body composition may help the physician identify LADA patients who require early insulin treatment in order to delay beta-cell exhaustion, as well those with increased CV risk due to excess truncal adiposity

    A Case of thyroid metastasis from pancreatic cancer: case report and literature review

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    Background: Thyroid metastases are clinically rare, and usually occur in patients with a history of prior malignancy and when there are metastases elsewhere. Metastases of pancreatic carcinoma to the thyroid are extremely rare, with only three cases reported in the literature.Case presentation: We report a patient who had a pancreatic carcinoma with metastasis to the thyroid as initial clinical presentation of the disease. A 63-year-old man with a history of weight loss and fatigue presented with cervical lymphadenopathies and a large nodule in the right lobe of the thyroid. A fine needle aspiration of the nodule gave inconclusive cytological results for the origin of the neoplastic cells. An ultrasound-guided core biopsy revealed the presence of a poorly differentiated adenocarcinoma infiltrating the thyroid with atrophic thyroid follicles. Immunohistochemical staining of the lesion was strongly positive for Cytokeratin 19 suggesting a pancreatic origin of the metastasis. A contrast CT scan demonstrated an enlargement of the pancreatic body, dilatation of the pancreatic duct, diffuse retroperitoneal, paraaortic and cervical lymphadenopathy and secondary lesions in the liver.Conclusion: Metastases to the thyroid from pancreatic carcinoma are extremely rare. A core biopsy of the lesion excluded a thyroid carcinoma and permitted the diagnosis of the primary neoplasm
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