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Jill Beech - One of the best experts on this subject based on the ideXlab platform.

  • investigation of single and paired measurements of adrenocorticotropic hormone for the diagnosis of pituitary Pars intermedia dysfunction in horses
    Journal of Veterinary Internal Medicine, 2015
    Co-Authors: David Rendle, Jill Beech, M Duz, T D H Parkin, A E Durham
    Abstract:

    Background Paired measurement of ACTH concentration may be more reliable than a single measurement. Hypothesis/Objectives To determine whether the mean of 2 measurements of ACTH concentration is more reliable in assessing pituitary Pars intermedia dysfunction (PPID) than a single measurement. Animals Paired ACTH measurements were performed on (1) 148 occasions from 124 horses being investigated for PPID, (2) 90 occasions from 76 horses with PPID that were receiving treatment with pergolide, and (3) 63 occasions from 50 horses in which there was no clinical suspicion of PPID. Histologic examination of the Pars intermedia was performed in 67 of the untreated horses. Methods Outcome of testing using single and the mean of paired samples was compared directly and both methods were compared against histology, which was considered the gold standard. Results Paired ACTH measurement altered binary classification as healthy or diseased in 6 of 211 cases, all off which had equivocal initial ACTH concentrations between 20 and 39 pg/mL. Using histology as the gold standard, optimal sensitivity and specificity for diagnosing PPID were 69.4 and 80.9%, respectively, for a single measurement and 72.2 and 76.2%, respectively, for paired measurements. The area under the receiver operating characteristic curve was 0.72 and 0.73 for single and paired measurements compared with histopathologic diagnosis, respectively. Conclusions and Clinical Importance Paired measurement of ACTH concentration offers no advantage over a single measurement.

  • evaluation of the effects of age and pituitary Pars intermedia dysfunction on corneal sensitivity in horses
    American Journal of Veterinary Research, 2013
    Co-Authors: Chelsey Miller, Mary L Utter, Jill Beech
    Abstract:

    Objective—To determine effects of age and pituitary Pars intermedia dysfunction (PPID) on corneal sensitivity in horses. Animals—20 adult horses allocated into 3 groups (PPID group, old [> 15 years old] horses with PPID [n = 5]; old group, old [> 15 years old] horses without PPID [9]; and young group, young [≤ 10 years old] horses without PPID [6]). All horses with PPID had hirsutism and abnormal fat deposition or laminitis; none of the old or young horses had hirsutism, abnormal fat deposition, or laminitis. Procedures—A Cochet-Bonnet aesthesiometer was used to measure the corneal touch threshold (CTT) in both eyes of each horse. The nylon monofilament was applied at a maximum length of 60 mm to the central region of the cornea and length was decreased by 5-mm increments until a consistent blink response was elicited. Tear production was assessed in all eyes via the Shirmer tear test (STT). Results—Mean ± SD CTT was significantly greater for young horses (47.50 ± 4.52 mm) than for horses in the old (28.0...

  • adrenocorticotropin concentration following administration of thyrotropin releasing hormone in healthy horses and those with pituitary Pars intermedia dysfunction and pituitary gland hyperplasia
    Javma-journal of The American Veterinary Medical Association, 2007
    Co-Authors: Jill Beech, Raymond C Boston, Sue Lindborg, Gail E Russell
    Abstract:

    Objective—To compare the effect of thyrotropin-releasing hormone (TRH) administration on endogenous ACTH concentrations in healthy horses and those with pituitary Pars inter-media hyperplasia and compare the test with the dexamethasone suppression test (DST). Design—Prospective case series. Animals—15 horses with clinical signs of pituitary Pars intermedia dysfunction (PPID), 4 horses with equivocal signs of PPID, and 29 horses without signs of PPID. Procedures—ACTH concentrations prior to and after administration of TRH were measured 61 times in 48 horses. Results of the DST (cortisol response) were compared with those of the TRH test in 29 horses. Thirty-three horses (24 with no clinical signs of PPID, 5 with clinical signs of PPID, and 4 with equivocal clinical signs of PPID) were euthanized and necropsied and their pituitary glands evaluated. Results—ACTH concentrations increased in all horses, but magnitude and duration of increase were significantly higher in horses with PPID. Endogenous ACTH concen...

  • alpha melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses horses with pituitary Pars intermedia dysfunction and equine Pars intermedia explants
    Domestic Animal Endocrinology, 2006
    Co-Authors: Dianne Mcfarlane, Jill Beech, Alastair Cribb
    Abstract:

    Thyrotropin releasing hormone (TRH) stimulates an increase in plasma cortisol in horses with Pars intermedia dysfunction (PPID, Cushing's disease). A similar phenomenon is observed in humans with Cushing's disease or Nelson's syndrome. The mechanism of the response in humans is not known, but an alteration in receptor expression, selectivity or responsiveness in abnormal corticotropes has been proposed. Horses with PPID, unlike humans, almost exclusively have adenomas of Pars intermedia (PI) rather than Pars distalis (PD) origin. Therefore, the mechanism responsible for the TRH response observed in horses likely differs. We proposed that TRH directly stimulates the PI in normal and PPID-affected horses to release proopiomelanocortin (POMC) derived peptides. Using alpha-melanocyte stimulating hormone (alpha-MSH) as a marker of a PI response and ACTH as a marker of a PD response, we were able to demonstrate a marked increase in plasma concentration of alpha-MSH and a modest, but significant increase in ACTH after TRH treatment in normal horses. The ability of TRH to directly stimulate release of POMC peptides was confirmed using PI and PD tissue explants. The presence of TRH receptor mRNA in PI tissue from both normal and PPID horses was confirmed using reverse transcriptase polymerase chain reaction. We conclude that TRH triggers the release of POMC-derived peptides from the PI through the direct stimulation of TRH receptors normally expressed on melanotropes. The increase in plasma cortisol following TRH in horses with PPID is likely attributable to the release of ACTH from the hyperplastic PI.

  • evaluation of suspected pituitary Pars intermedia dysfunction in horses with laminitis
    Javma-journal of The American Veterinary Medical Association, 2004
    Co-Authors: Mark T Donaldson, Alec J R Jorgensen, Jill Beech
    Abstract:

    Objective—To determine prevalence and clinical features of pituitary Pars intermedia dysfunction (PPID) in horses with laminitis. Design—Case series. Animals—40 horses with laminitis. Procedures—Horses with laminitis that survived an initial episode of pain and were not receiving medications known to alter the hypothalamic-pituitary-adrenal axis were tested for PPID by evaluation of endogenous plasma ACTH concentration. Signalment, suspected cause, month of onset and duration of laminitis, Obel grade of lameness, pedal bone rotation, physical examination findings, results of endocrine function tests, treatment, outcome, and postmortem examination findings were recorded. Results—Prevalence of PPID as defined by a single high plasma ACTH concentration was 70%. Median age of horses suspected of having PPID (n = 28) was 15.5 years, and median age of horses without PPID (12) was 14.5 years. Laminitis occurred most frequently in horses with and without suspected PPID during September and May, respectively. Chro...

Dianne Mcfarlane - One of the best experts on this subject based on the ideXlab platform.

  • pathophysiology and clinical features of pituitary Pars intermedia dysfunction
    Equine Veterinary Education, 2014
    Co-Authors: Dianne Mcfarlane
    Abstract:

    Summary Our understanding of the development and progression of equine pituitary Pars intermedia (PI) dysfunction has expanded over the last decade, although much remains to be explained. Degeneration of the hypothalamic periventricular dopaminergic neurons results in disinhibition of the endocrine cells of the PI, the melanotropes. As a result, the PI enlarges, compressing the adjacent lobes, the Pars distalis and Pars nervosa. The disinhibited melanotropes overproduce pro-opiomelanocortin peptides, including α-melanocyte stimulating hormone, β-endorphin, corticotrophin-like intermediate lobe peptide and adrenocorticotropin. The excess in PI hormones, perhaps in concert with a deficiency in other pituitary hormones, results in clinical signs of pituitary PI dysfunction. Evidence suggests both oxidative stress and accumulation of misfolded neuronal proteins contribute to damage to the periventricular neurons, although it is not clear if these pathologies actually initiate the disease or are downstream events.

  • equine pituitary Pars intermedia dysfunction
    Veterinary Clinics of North America-equine Practice, 2011
    Co-Authors: Dianne Mcfarlane
    Abstract:

    Equine pituitary Pars intermedia dysfunction (PPID), also known as equine Cushing's syndrome, is a widely recognized disease of aged horses. Over the past two decades, the aged horse population has expanded significantly and in addition, client awareness of PPID has increased. As a result, there has been an increase in both diagnostic testing and treatment of the disease. This review focuses on the pathophysiology and clinical syndrome, as well as advances in diagnostic testing and treatment of PPID, with an emphasis on those findings that are new since the excellent comprehensive review by Schott in 2002.

  • Fecal egg counts after anthelmintic administration to aged horses and horses with pituitary Pars intermedia dysfunction
    Journal of the American Veterinary Medical Association, 2010
    Co-Authors: Dianne Mcfarlane, Grace M Hale, Eileen Johnson, Lara K. Maxwell
    Abstract:

    Objective—To determine effects of pituitary Pars intermedia dysfunction (Cushing's disease) and age on fecal egg count and time to egg reappearance after anthelmintic treatment in horses residing in similar environments. Design—Cross-sectional study. Animals—29 healthy horses (4 to 35 years old) and 13 horses with PPID (13 to 33 years old). Procedures—Fecal egg counts were performed by use of a modified Wisconsin flotation method at 2-week intervals before and after ivermectin treatment. Results—Horses with PPID had higher fecal egg counts before and 8, 10, and 12 weeks after ivermectin treatment, compared with counts for site-matched healthy horses. There was no difference in the period for < 90% reduction in fecal egg counts between the 2 groups. Age did not affect fecal egg counts at any time point. Conclusions and Clinical Relevance—For similar environmental conditions, horses with PPID were more likely to have higher fecal egg counts than were healthy horses. Therefore, horses with PPID may need to h...

  • extrapituitary and pituitary pathological findings in horses with pituitary Pars intermedia dysfunction a retrospective study
    Journal of Equine Veterinary Science, 2009
    Co-Authors: Christiana M Glover, Noel Dybdal, Lisa M Miller, Alfonso Lopez, Wendy M Duckett, Dianne Mcfarlane
    Abstract:

    Abstract The objective of this study was to describe the histopathologic changes observed in extrapituitary organs as well as the pituitary glands of horses with pituitary Pars intermedia dysfunction (PPID). Adrenal gland, thyroid gland, liver, lung, kidney, heart, and pituitary gland from 32 horses with clinical and histologic evidence of PPID and 20 control horses were reviewed histologically. Ten of the control horses were aged animals (≥15 years), allowing those changes attributed to age to be identified. In addition to previously reported changes in adrenal gland and liver, an association was established between PPID and several extrapituitary histopathologic changes, namely bronchiolitis, proliferative glomerulopathy, and myocardial lipofuscinosis and fibrosis. The potential biologic significance of these changes is discussed and, although the retrospective design of the current study precludes establishment of causal relationships between the observed extrapituitary changes and PPID, these findings suggest that further investigations are warranted.

  • cytokine dysregulation in aged horses and horses with pituitary Pars intermedia dysfunction
    Journal of Veterinary Internal Medicine, 2008
    Co-Authors: Dianne Mcfarlane, Todd C Holbrook
    Abstract:

    Background: Equine pituitary Pars intermedia dysfunction (PPID) is the result of a loss of dopaminergic inhibition of the Pars intermedia secondary to neurodegeneration of periventricular hypothalamic neurons. The pathologic events contributing to development of neurodegeneration or clinical signs in equids with PPID are unknown. Chronic inflammation may contribute to initiation or progression of PPID. Hypothesis: Horses with PPID have a distinct systemic cytokine profile compared with that of normal adult or aged horses. The cytokine profile of healthy aged horses differs from that of adult horses. Animals: Aged horses with PPID, healthy aged-matched controls, and adult controls (n = 14 per group). Methods: Total leukocyte cytokine expression was determined by quantitative polymerase chain reaction (PCR), and tumor necrosis factor (TNF)-α plasma concentration was determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF-α response after endotoxin (lipopolysaccharide [LPS]) treatment was assessed by ELISA. Results: Aged healthy horses had increased expression of interleukin (IL)-6, IL-8, and interferon-γ as well as PBMC TNF-α release after LPS stimulation compared with healthy adult horses. In contrast, aged horses with PPID had increased IL-8 expression, but expression of other cytokines was similar to that of healthy adult horses, not age-matched controls. Conclusions and Clinical Importance: Aged horses show evidence of a proinflammatory state that may contribute to development of age-associated diseases. Horses with PPID have increased expression of IL-8, which may influence the ability of horses with PPID to respond to bacterial pathogens. The general decrease in proinflammatory cytokine expression observed in horses with PPID may be the outcome of high plasma concentrations of anti-inflammatory hormones.

Fabian Mohamed - One of the best experts on this subject based on the ideXlab platform.

Mark T Donaldson - One of the best experts on this subject based on the ideXlab platform.

  • nitration and increased alpha synuclein expression associated with dopaminergic neurodegeneration in equine pituitary Pars intermedia dysfunction
    Journal of Neuroendocrinology, 2005
    Co-Authors: Dianne Mcfarlane, Mark T Donaldson, Noel Dybdal, Lisa Miller, Alastair E Cribb
    Abstract:

    Equine pituitary Pars intermedia dysfunction (PPID) is a spontaneously occurring progressive disease affecting aged horses and ponies. The pathogenesis of PPID is poorly understood, but the available evidence supports a loss of dopaminergic inhibition of the melanotropes of the Pars intermedia. Horses with PPID have increased plasma concentrations of Pars intermedia pro-opiomelanocortin-derived peptides that decrease in response to dopamine or dopamine agonist administration. Dopamine and dopamine metabolite concentrations are decreased in the Pars intermedia of affected horses compared to age-matched control horses. Horses with disease that are treated with the dopamine agonist pergolide show improvement in clinical signs and normalisation of diagnostic test results. In the present study, immunohistochemical evaluation of pituitary and hypothalamic tissue demonstrated reduced tyrosine hydroxylase immunoreactivity in affected horses compared to age-matched and young controls, supporting the role of dopaminergic neurodegeneration in PPID. In addition, immunohistochemical evaluation revealed an increase in the oxidative stress marker, 3-nitrotyrosine and in nerve terminal protein, alpha-synuclein that colocalised in the Pars intermedia of horses with disease. These findings suggest a role for nitration of overexpressed alpha-synuclein in the pathogenesis of neurodegeneration in PPID.

  • evaluation of suspected pituitary Pars intermedia dysfunction in horses with laminitis
    Javma-journal of The American Veterinary Medical Association, 2004
    Co-Authors: Mark T Donaldson, Alec J R Jorgensen, Jill Beech
    Abstract:

    Objective—To determine prevalence and clinical features of pituitary Pars intermedia dysfunction (PPID) in horses with laminitis. Design—Case series. Animals—40 horses with laminitis. Procedures—Horses with laminitis that survived an initial episode of pain and were not receiving medications known to alter the hypothalamic-pituitary-adrenal axis were tested for PPID by evaluation of endogenous plasma ACTH concentration. Signalment, suspected cause, month of onset and duration of laminitis, Obel grade of lameness, pedal bone rotation, physical examination findings, results of endocrine function tests, treatment, outcome, and postmortem examination findings were recorded. Results—Prevalence of PPID as defined by a single high plasma ACTH concentration was 70%. Median age of horses suspected of having PPID (n = 28) was 15.5 years, and median age of horses without PPID (12) was 14.5 years. Laminitis occurred most frequently in horses with and without suspected PPID during September and May, respectively. Chro...

  • treatment with pergolide or cyproheptadine of pituitary Pars intermedia dysfunction equine cushing s disease
    Journal of Veterinary Internal Medicine, 2002
    Co-Authors: Mark T Donaldson, Bernadette H Lamonte, Peter R Morresey, Gary Smith, Jill Beech
    Abstract:

    Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary Pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 microg/kg p.o. q24h (range, 1.7-5.5 microg/kg). All horses treated with cyproheptadine were given 0.25 mg/kg p.o. q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml; range, 4.2-173) were significantly lower (P < .01) than those in horses treated with cyproheptadine (n = 7; median = 141.0 pg/ml: range, 10-1,230). Among horses treated with pergolide, there was a correlation between ACTH concentration after treatment and the duration of treatment (P < .001) and pergolide dose (P = .04). Significantly (P = .02) more owners of horses treated with pergolide (85%, 17/20) reported an improvement in clinical signs compared to owners of horses treated with cyproheptadine (28%, 2/7).

  • treatment with pergolide or cyproheptadine of pituitary Pars intermedia dysfunction equine cushing s disease
    Journal of Veterinary Internal Medicine, 2002
    Co-Authors: Mark T Donaldson, Bernadette H Lamonte, Peter R Morresey, Gary Smith, Jill Beech
    Abstract:

    Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary Pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucoseconcentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 μg/kg PO q24h (range, 1.7-5.5 μg/kg). All horses treated with cyproheptadine were given 0.25 mg/kg PO q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml; range, 4.2-173) were significantly lower (P <.01) than those in horses treated with cyproheptadine (n = 7; median = 141.0 pg/ml; range, 10-1,230). Among horses treated with pergolide, there was a correlation between ACTH concentration after treatment and the duration of treatment (P < .001) and pergolide dose (P =.04). Significantly (P =.02) more owners of horses treated with pergolide (85%, 17/20) reported an improvement in clinical signs compared to owners of horses treated with cyproheptadine (28%, 2/7). Kev words: ACTH; Hyperadrenocorticism; Pituitary adenoma; Pituitary dysfunction; Pituitary hyperplasia; Pituitary tumor.

Mariano Acosta - One of the best experts on this subject based on the ideXlab platform.