General

Elevated alp in dogs

Elevated alp in dogs

Elevated alp in dogs with Cushing's disease

Introduction {#vru12847-sec-0010}

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Canine Cushing's disease (CD) is a hypercortisolism, caused by increased ACTH production by an ACTH‐secreting pituitary adenoma. As in human Cushing's disease, CD is a systemic disorder resulting in a variety of clinical signs depending on the presence of endocrinopathies, such as hypoadrenocorticism, hypoglycemia, and hypothyroidism.[1](#vru12847-bib-0001){ref-type="ref"}, [2](#vru12847-bib-0002){ref-type="ref"} Hyperglycemia and insulin resistance (IR) are commonly associated with the CD[3](#vru12847-bib-0003){ref-type="ref"}, [4](#vru12847-bib-0004){ref-type="ref"}, [5](#vru12847-bib-0005){ref-type="ref"}, [6](#vru12847-bib-0006){ref-type="ref"}, [7](#vru12847-bib-0007){ref-type="ref"}, [8](#vru12847-bib-0008){ref-type="ref"}, [9](#vru12847-bib-0009){ref-type="ref"} and are related to the overproduction of cortisol.[10](#vru12847-bib-0010){ref-type="ref"} Hyperinsulinemia is also present, and is correlated with cortisol overproduction and hypercortisolism.[11](#vru12847-bib-0011){ref-type="ref"} IR is also a major risk factor for the development of diabetes mellitus.[12](#vru12847-bib-0012){ref-type="ref"}, [13](#vru12847-bib-0013){ref-type="ref"}

The gold standard method of diagnosis of CD is via the detection of an ACTH‐secreting pituitary adenoma by pituitary imaging using conventional and dynamic MRI. However, imaging is expensive and cannot be used to identify ACTH‐producing lesions in all animals. Therefore, the development of a serum‐based biomarker is advantageous. The determination of serum cortisol has been utilized as an objective measure to confirm the diagnosis and severity of CD in humans and dogs. However, the measurement of serum cortisol in the canine setting is prone to considerable variability, due to diurnal variations in cortisol secretion, which are more variable and pronounced in dogs, compared to humans. In addition, there is great individual variability in serum cortisol concentrations, and consequently, the use of a single serum cortisol concentration for diagnosis or staging of CD can be problematic.[14](#vru12847-bib-0014){ref-type="ref"} In addition, serum cortisol levels can be affected by multiple factors, such as time of day, fasting, stress, breed, and diet.[14](#vru12847-bib-0014){ref-type="ref"}, [15](#vru12847-bib-0015){ref-type="ref"}, [16](#vru12847-bib-0016){ref-type="ref"} Therefore, a more reliable marker is needed for the diagnosis of CD.

Albumin is a low molecular weight protein that functions to maintain intravascular osmotic pressure. Because of its small molecular weight, albumin can cross the blood‐brain barrier. Altered serum albumin has been reported in a variety of human neurological disorders.[17](#vru12847-bib-0017){ref-type="ref"}, [18](#vru12847-bib-0018){ref-type="ref"}, [19](#vru12847-bib-0019){ref-type="ref"}, [20](#vru12847-bib-0020){ref-type="ref"} In addition, there is evidence that serum albumin is altered in the presence of various forms of Cushing's disease in humans, as well as in canine CD.[20](#vru12847-bib-0020){ref-type="ref"}, [21](#vru12847-bib-0021){ref-type="ref"} The purpose of this study was to assess the role of serum albumin as a marker of CD in dogs. Specifically, we evaluated the role of serum albumin as a diagnostic biomarker and a marker of disease severity in dogs with CD.

Materials and Methods {#vru12847-sec-0020}

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The study population consisted of 41 client‐owned dogs presenting to the UC Davis Veterinary Medical Teaching Hospital between January 2017 and June 2017, and dogs referred to the University of California, Davis Animal Care and Use Committee. All dogs had clinical signs consistent with a diagnosis of Cushing's disease (CD) including lethargy, polyuria, polydipsia, hyperglycemia, and generalized muscle wasting. All dogs had serum cortisol concentrations greater than 50 nmol/L, as confirmed via laboratory analysis at the Veterinary Medical Teaching Hospital. All CD dogs were euthanized for reasons unrelated to the current study, while 20 of these 41 dogs were included in the final dataset. Inclusion criteria consisted of the following: a confirmed diagnosis of CD, with all dogs presenting with Cushing's syndrome, as confirmed via positive serum cortisol, consistent clinical signs, and negative response to a negative control, a positive response to a positive control, or presence of an ACTH‐secreting pituitary adenoma on MRI (if available). The control group included dogs that were healthy and had normal clinical exam results, as well as a negative serum cortisol concentration. All dogs were fasted for 24 hours before the blood draw.

The clinical chemistry profile, serum biochemical


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