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      Cushing’s syndrome—an epidemiological study based on a canine population of 21,281 dogs

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          Abstract

          The epidemiological characteristics of spontaneous hypercortisolism (HC) were derived from 21,281 client-owned dogs selected from four private veterinary clinics and one university reference center for endocrinology. The odds ratio (OR) method was employed to investigate the risk of developing HC related to breed, gender, and sexual status. The estimated prevalence of HC in the four private clinics was 0.20% [95% confidence interval (CI), 0.13–0.27] and was significantly different compared to the university reference center (1.46%; 95% CI, 1.12–1.80). Sex, breed, and age resulted in risk factors for HC. Mean (± SD) age for dogs with HC was 9.8 (± 2.5) yr. Females had higher risk for HC compared to males (OR 1.85; 95% CI, 1.24–2.75); all neutered dogs (both males and females) had higher risk than intact dogs (OR 2.54; 95% CI, 1.72–3.73); and neutered females had higher risk compared to intact females (OR 2.61; 95% CI, 1.54–4.42). Using the mixed breed dogs as a control population (OR = 1), the risk of developing HC was significantly higher in the Standard Schnauzer (OR 58.1; p < 0.0001) and Fox Terrier (OR 20.33; p < 0.0001).

          With regard to HC, this study identified an overall prevalence of 0.20%. The data support the existence of sex predisposition, with the highest risk for neutered females.

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          Most cited references34

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          Incidence and late prognosis of cushing's syndrome: a population-based study.

          The main purpose was to assess the incidence and late outcome of Cushing's syndrome, particularly in Cushing's disease. Information for all patients diagnosed with Cushing's syndrome during an 11-yr period in Denmark was retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease), 0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease, 11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33]. The SMR was partly attributable to an increased mortality within the first year after diagnosis. Eight patients died before treatment could be undertaken. The prognosis in patients with malignant disease was very poor. Patients in whom more than 5 yr had elapsed since initial surgery were studied separately, including a questionnaire on their perceived quality of health. In 45 patients with Cushing's disease who had been cured through transsphenoidal neurosurgery, only 1 had died (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived quality of health was significantly impaired only in patients with Cushing's disease and appeared independent of disease control or presence of hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is associated with increased mortality, in patients with no concurrent malignancy also; 2) the excess mortality was mainly observed during the first year of disease; and 3) the impaired quality of health in long-term survivors of Cushing's disease is not fully explained.
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            Cushing's syndrome.

            During the past 30 years, there have been advances in understanding of the pathogenesis of Cushing's syndrome and in differential diagnosis of its various forms. Improved diagnostic tests and procedures have increased the ability to recognise even mild hypercortisolism and have provided the means to obtain an accurate diagnosis. Despite these advances, the occurrence of unusual clinical presentations and laboratory shortcomings may produce diagnostic problems and challenge clinical intuition. This article reviews recent pathogenic views, new tests, and new diagnostic problems in the evaluation of Cushing's syndrome. Atypical clinical presentations of hypercortisolism and some laboratory shortcomings that may confuse the diagnosis of Cushing's syndrome are also reported.
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              Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome.

              The mechanism by which cortisol is produced in adrenal Cushing's syndrome, when ACTH is suppressed, was previously unknown and was referred to as being "autonomous." More recently, several investigators have shown that some cortisol and other steroid-producing adrenal tumors or hyperplasias are under the control of ectopic (or aberrant, illicit, inappropriate) membrane hormone receptors. These include ectopic receptors for gastric inhibitory polypeptide (GIP), beta-adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT4), or possibly leptin. The presence of aberrant receptors places adrenal cells under stimulation by a trophic factor not negatively regulated by glucocorticoids, leading to increased steroidogenesis and possibly to the proliferative phenotype. The molecular mechanisms responsible for the abnormal expression and function of membrane hormone receptors are still largely unknown. Identification of the presence of these illicit receptors can eventually lead to new pharmacological therapies as alternatives to adrenalectomy, now demonstrated by the long-term control of ectopic P-AR- and LH/hCGR-dependent Cushing's syndrome by propanolol and leuprolide acetate. Further studies will potentially identify a larger diversity of hormone receptors capable of coupling to G proteins, adenylyl cyclase, and steroidogenesis in functional adrenal tumors and probably in other endocrine and nonendocrine tumors.
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                Author and article information

                Journal
                Open Vet J
                Open Vet J
                Open Veterinary Journal
                Faculty of Veterinary Medicine (Tripoli, Libya )
                2226-4485
                2218-6050
                April 2019
                15 February 2019
                : 9
                : 1
                : 27-32
                Affiliations
                [1 ]Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell’Emilia, Bologna 40064, Italy
                [2 ]Ospedale Veterinario I Portoni Rossi, Zola Predosa, Bologna 40069, Italy
                [3 ]Ospedale Veterinario Pingry, Bari 70126, Italy
                [4 ]Centro Veterinario Bolognese, Bologna 40131, Italy
                [5 ]Ambulatorio Veterinario Schiavi, Udine 33100, Italy
                Author notes
                [* ] Corresponding Author: Federico Fracassi. Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell’Emilia, Bologna 40064, Italy. federico.fracassi@ 123456unibo.it
                Article
                OpenVetJ-9-27
                10.4314/ovj.v9i1.5
                6500859
                31086762
                84a19df4-d6b6-4740-8d30-de4b82bbe8f2
                Copyright @ 2019

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 August 2018
                : 23 January 2019
                Categories
                Original Research

                cortisol,hyperadrenocorticism,hypercortisolism,pdh
                cortisol, hyperadrenocorticism, hypercortisolism, pdh

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