Search

Background: Equine pituitary pars intermedia dysfunction (PPID) is treated with daily pergolide therapy. Owner compliance and its effect on PPID control have not been previously investigated., Methods: Clinical records were searched to identify the sample of animals with PPID treated with pergolide from 2016 to 2019. The signalment was noted and the dose of pergolide received calculated. Animals were classified as compliant (receiving ≥90% of the veterinarian recommended dose of pergolide) or non-compliant, and as controlled (follow-up basal adrenocorticotrophic hormone concentrations within the reference range) or not., Results: In total, 110 animals were included. The majority (85%) were ≥16 years (mean ± SD 19.8 ± 4.4 years); the most common breeds were Cob (18%), Thoroughbred (16%) and Welsh (15%); 37% were female and 63% male. Overall, 48% were compliant and 52% non-compliant. There was no significant effect of compliance on laboratory control. Of those that were compliant, 74% were controlled, while 67% of non-compliant animals were controlled. Univariable analysis revealed a significant (p < 0.001) effect of age and breed on compliance and control, and of sex on control. On multivariable analysis, only age (compliance) and breed (compliance and control) were retained in the final model., Conclusion: Only half of animals received the recommended pergolide dose; however, this did not affect laboratory control of PPID., (© 2021 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Pituitary pars intermedia dysfunction (PPID) is the most prevalent endocrine disorder of older equids. To date, key research areas likely to have the greatest impact on equine health have not been identified. In human medicine, public and patient involvement is widely used to inform research agendas. This study aimed to engage with veterinary surgeons and horse owners to identify evidence gaps ('uncertainties') and prioritise these into a list of the 10 most important PPID research questions. The James Lind Alliance (JLA) Priority Setting Partnership (PSP) Framework was adapted. Questions about the diagnosis, treatment and prognosis of PPID were gathered via an online survey targeting veterinary surgeons and horse owners with experience of PPID. Thematic analysis was used to form a longlist of collated indicative research questions (CIRQs), defined by the JLA as true 'evidence uncertainties' when not answered by a published, clinically relevant, up-to-date systematic review. In an interim prioritisation survey, questions were ranked by weighted scores creating a shortlist of 25 that were taken forward to the PSP workshop, where participants reached a consensus on the top 10. Useable responses containing ≥1 question were received from 524 respondents (92.6% owners, n = 485; 7.4% veterinary surgeons, n = 39). After screening for relevance, 1,260 individual questions were included in thematic analysis, resulting in 47 CIRQs. Interim prioritisation votes for the CIRQs were received from 360 respondents. The top 10 questions prioritised at the PSP workshop focused on long-term prognosis, diagnostic accuracy, efficacy of pergolide treatment, alternative treatment/management strategies and potential treatment options for poor responders to pergolide. The quantity of questions generated indicates an extensive number of uncertainties regarding the diagnosis, treatment and prognosis of PPID. The top 10 research questions will help to inform key areas for evidence synthesis and knowledge translation, and to direct future research into areas most important to end users involved in caring for and treating animals with PPID., Competing Interests: As a collaborator Boehringer Ingelheim Animal Health UK Limited part funded this study, however, their only involvement in the priority setting partnership was to help disseminate the initial questionnaire to relevant participants. Both JI and CM have previously received funding for other specific equine endocrinology research projects from Boehringer Ingelheim Animal Health. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors have no financial or personal relationships with other people or organisations that could inappropriately influence or bias the content of the paper.

Background: Hyperinsulinaemia is the suspected component of insulin dysregulation having the strongest association with laminitis and occurs variably in equids with pituitary pars intermedia dysfunction (PPID)., Objectives: We hypothesised that magnitude of hyperinsulinaemia correlates with laminitis severity in PPID-affected equids. Furthermore, we hypothesised that owners can be unaware of chronic endocrinopathic laminitis., Study Design: Cross-sectional study., Methods: Serum insulin concentrations, owner-reported laminitis history and radiographic evidence of laminitis were determined in 38 client-owned horses and ponies with confirmed PPID. Laminitis severity was classified into four categories (normal [nonlaminitic], mild, moderate or severe laminitis) based on degree of distal phalangeal rotation. Animals were also categorised as normoinsulinaemic (<20 μU/ml), mildly hyperinsulinaemic (20-50 μU/ml) and severely hyperinsulinaemic (>50 μU/ml). One-way ANOVA, t tests and Fisher's exact tests were performed., Results: While owners reported laminitis in 37% of animals, 76% were laminitic based on study criteria (P = 0.01). Owners reported laminitis more frequently in hyperinsulinaemic vs. normoinsulinaemic animals; recognition increased with severity of hyperinsulinaemia (P = 0.03). Mean insulin concentrations were higher in equids with moderate to severe radiographic laminitis (geometric mean 74.1, 95% confidence interval (CI) 38.4-143.1 uU/ml) vs. those classified radiographically as normal to mild (31.9, 95% CI 21.1-48.1 uU/ml P = 0.03)., Main Limitations: Dynamic insulin testing was not performed; some normoinsulinaemic animals might have had subtle insulin dysregulation., Conclusions: Although radiographic abnormalities were present in most animals at the time of PPID diagnosis, chronic laminitis remained unrecognised by many owners. Owner awareness of laminitis increased with severity of hyperinsulinaemia and higher insulin concentrations were detected in association with more severe radiographic changes. The Summary is available in Chinese - See Supporting Information., (© 2018 EVJ Ltd.)

The purpose of this article is to provide a review of the current knowledge and opinions about the epidemiology, clinical findings (including sequelae), diagnosis, treatment and monitoring of equine pituitary pars intermedia dysfunction, particularly in the Australian context. This information and the recommendations provided will assist practitioners in making informed decisions regarding the diagnosis and management of this disorder., (© 2018 Australian Veterinary Association.)

Pituitary pars intermedia dysfunction (PPID), also known as equine Cushing's disease, is widely reported in middle-aged to older domestic equids but to date reported in only one nondomestic equid, the onager ( Equus hemionus onager). This case series reports clinical, hematological, and pathological findings consistent with PPID in two further equid species: one Chapman's zebra ( Equus quagga chapmani) and five Przewalski's horses ( Equus ferus przewalskii). The case series reports basal adrenocorticotropic hormone (ACTH) testing as a method to diagnose and monitor PPID in zoological equids and the use of pergolide mesylate to reduce basal ACTH concentration and reduce clinical signs associated with PPID. Gross and histopathological examinations of the pituitary gland in four of these cases revealed either pars intermedia adenomas or adenomatous hyperplasia, similar to pathological findings in domestic equids affected by PPID. These findings suggest that clinicians working with nondomestic equids should be aware of this condition and consider screening for it routinely, particularly given that improvements in management and veterinary care for exotic animals are resulting in a more aged captive population. Early diagnosis and treatment of PPID may prevent the development of painful clinical sequelae and therefore improve the welfare of zoo equids.

OBJECTIVE To identify signs of tissue-specific cortisol activity in samples of suspensory ligament (SL) and neck skin tissue from horses with and without pituitary pars intermedia dysfunction (PPID). SAMPLE Suspensory ligament and neck skin tissue samples obtained from 26 euthanized horses with and without PPID. PROCEDURES Tissue samples were collected from 12 horses with and 14 horses without PPID (controls). Two control horses had received treatment with dexamethasone; data from those horses were not used in statistical analyses. The other 12 control horses were classified as old horses (≥ 14 years old) and young horses (≤ 9 years old). Standard histologic staining, staining for proteoglycan accumulation, and immunostaining of SL and neck skin tissue sections for glucocorticoid receptors, insulin, 11β hydroxysteroid dehydrogenase type 1, and 11β hydroxysteroid dehydrogenase type 2 were performed. Findings for horses with PPID were compared with findings for young and old horses without PPID. RESULTS Compared with findings for old and young control horses, there were significantly more cells stained for glucocorticoid receptors in SL samples and for 11 β hydroxysteroid dehydrogenase type 1 in SL and skin tissue samples from horses with PPID. Insulin could not be detected in any of the SL or skin tissue samples. Horses with PPID had evidence of SL degeneration with significantly increased proteoglycan accumulation. Neck skin tissue was found to be significantly thinner in PPID-affected horses than in young control horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that tissue-specific dysregulation of cortisol metabolism may contribute to the SL degeneration associated with PPID in horses.

OBJECTIVE To compare tear cortisol concentrations between horses and ponies with pituitary pars intermedia dysfunction (PPID) and healthy nonaged (≤ 15 years old) and aged (≥ 20 years old) horses and to determine whether serum and tear cortisol concentrations were correlated. ANIMALS 11 horses and ponies with PPID and 20 healthy control horses and ponies (11 nonaged and 9 aged). PROCEDURES Paired tear and serum samples were obtained from PPID and control animals. All animals were free of active ocular disease. Tear and serum cortisol concentrations were measured with an ELISA and chemiluminescent assay, respectively. Groups were compared with Kruskal-Wallis and Mann-Whitney U tests, and Spearman correlation analysis was used to examine relationships between tear and serum cortisol concentrations within groups. RESULTS Median tear cortisol concentration was significantly higher in PPID animals than in aged control animals, despite comparable serum cortisol concentrations in PPID and aged control animals. Median tear-to-serum cortisol concentration ratios were also significantly higher in PPID animals than in aged control animals. Serum and tear cortisol concentrations were not significantly correlated in PPID or control animals. CONCLUSIONS AND CLINICAL RELEVANCE Some horses and ponies with PPID had increased tear cortisol concentrations, compared with concentrations in healthy aged animals. Localized cortisol production in the tear film or altered cortisol binding dynamics could have contributed to this increase. Further studies are warranted to evaluate these mechanisms and to determine whether increased tear cortisol concentrations are associated with delays in corneal wound healing in horses and ponies with and without PPID.

OBJECTIVE To assess effects of withholding feed on thyrotropin-releasing hormone (TRH) stimulation test results used in diagnosis of pituitary pars intermedia dysfunction in horses and determine effects of combined testing on results of the TRH stimulation test and the oral sugar test (OST) used in diagnosis of equine metabolic syndrome. ANIMALS 30 adult horses. PROCEDURES All horses underwent TRH stimulation tests under fed and nonfed conditions, an OST alone, and an OST combined with TRH stimulation testing. For TRH stimulation tests, plasma ACTH concentrations were measured before (baseline) and 10 minutes after (poststimulation) IV TRH administration. For the OST, plasma glucose and insulin concentrations were measured before (baseline) and 60 and 90 minutes after oral corn syrup administration. For combined testing, the TRH stimulation test was initiated immediately after 60-minute posttreatment sample collection for the OST. Results were compared among methods by Wilcoxon matched-pairs, signed rank tests, paired t tests, and Bland-Altman analysis. RESULTS Feeding conditions did not affect median ACTH concentrations when TRH stimulation tests were performed alone. Median baseline ACTH concentration did not differ between TRH stimulation tests performed alone (under fed or nonfed conditions) and those combined with OSTs. Median poststimulation ACTH concentration was significantly lower for combined tests than for solitary TRH stimulation tests. Mean 60-minute plasma glucose concentration was significantly lower for solitary OSTs than for combined tests, but this difference could not be attributed to TRH administration. CONCLUSIONS AND CLINICAL RELEVANCE Combined testing in the manner described impacted ACTH concentrations during TRH stimulation tests and is not recommended at this time.

Background: Equine pituitary pars intermedia dysfunction (PPID) may be diagnosed by measuring baseline plasma adrenocorticotrophic hormone (ACTH). The Immulite 1000 analyzer uses an automated chemiluminescence enzyme assay, previously validated for measuring equine ACTH. Recently, an automated bench-top immunoassay analyzer (AIA-360), designed for analytes in people, became available for veterinary use., Objectives: Objectives were to evaluate analytic performance of the AIA immunoassay for measuring equine ACTH, and compare the results with those obtained by the Immulite., Methods: Adrenocorticotrophic hormone was measured in plasma samples from 52 clinical cases. For the AIA, within- and between-run coefficients of variation (CV) were assessed, linearity and recovery studies performed, and observed total error (TEobs ) calculated. Correlation and agreement between the 2 analyzers were also evaluated., Results: Within-run and between-run CV of the AIA ranged from 2.3% to 4% and 3.5% to 8%, respectively. ACTH recoveries ranged from 89.5% to 115.9%. TEobs at 26.5 pg/mL ACTH was 4.1 pg/mL. The ACTH results (median: 25.9 pg/mL; range: 4.3-276.7 pg/mL) with AIA were significantly lower (P < .0001) than with the Immulite (median: 29.9 pg/mL; range: 10.3-639.0 pg/mL). Correlation between the 2 analyzers was r = 0.882 (P < .0001), with a significant bias for the AIA of -16 pg/mL. The 2 methods were not identical within inherent imprecision., Conclusion: The AIA is precise for measuring ACTH in horses. Although correlation between the instruments is good, the values obtained by the immunoassays cannot be used interchangeably and should be interpreted using reference intervals established for each analyzer to avoid false negatives. Diagnostic sensitivity and specificity of the AIA-360 should be evaluated before clinical use., (© 2016 American Society for Veterinary Clinical Pathology.)

Objective: To compare whole-body phenylalanine kinetics and the abundance of factors in signaling pathways associated with skeletal muscle protein synthesis and protein breakdown between horses with pituitary pars intermedia dysfunction (PPID) and age-matched control horses without PPID., Animals: 12 aged horses (6 horses with PPID and 6 control horses; mean age, 25.0 and 25.7 years, respectively)., Procedures: Plasma glucose, insulin, and amino acids concentrations were determined before and 90 minutes after feeding. Gluteal muscle biopsy samples were obtained from horses 90 minutes after feeding, and the abundance and activation of factors involved in signaling pathways of muscle protein synthesis and breakdown were determined. The next day, horses received a priming dose and 2 hours of a constant rate infusion of (13)C sodium bicarbonate followed by a priming dose and 4 hours of a constant rate infusion of 1-(13)C phenylalanine IV; whole-body protein synthesis was determined., Results: Plasma glucose and insulin concentrations were higher after feeding than they were before feeding for both groups of horses; however, no significant postprandial increase in plasma amino acids concentrations was detected for either group. Phenylalanine flux, oxidation, release from protein breakdown, and nonoxidative disposal were not significantly different between groups. No significant effect of PPID status was detected on the abundance or activation of positive or negative regulators of protein synthesis or positive regulators of protein breakdown., Conclusions and Clinical Relevance: Results of this study suggested that whole-body phenylalanine kinetics and the postprandial activation of signaling pathways that regulate protein synthesis and breakdown in muscles were not affected by PPID status alone in aged horses.

Background: Pituitary pars intermedia dysfunction (PPID) is common in older horses., Objectives: To determine diagnosis frequency, prognostic factors, long-term survival, and owner satisfaction with treatment., Animals: Medical records from horses diagnosed with PPID, 1993-2004., Methods: A retrospective cohort design with data collected from the Veterinary Medical Data Base (VMDB) and a cohort of 3 VTHs. Proportional accessions, annual incidence, and demographics were compared for all accessions. During the same period, a subset of medical records (n = 44) was extracted and owners (n = 34) contacted to obtain long-term follow-up information., Results: Diagnoses of PPID were reported for 217 horses that presented to VTHs and were reported to the VMDB. Proportional diagnosis increased from 0.25/1,000 in 1993 to 3.72/1,000 in 2002. For 44 horses included in the follow-up study, the most commons signs were hirsutism (84%) and laminitis (50%). Of 34 horse owners contacted, the average time from onset of signs to diagnosis was 180 days. Improvement in ≥ 1 signs, 2 months after diagnosis, was reported by 9/22 (41%) of horse owners. Clinical signs and clinicopathologic data were not associated with survival, and 50% of horses were alive 4.6 years after diagnosis. Cause of death among horses (15/20; 85%) was euthanasia, and 11/15 (73%) were euthanized because of conditions associated with PPID. Most horse owners (28/29; 97%) said they would treat a second horse for PPID., Conclusion and Clinical Importance: PPID was diagnosed with increasing frequency, and 50% of horses survived 4.5 years after diagnosis. Owners were satisfied with their horses' quality of life and would treat a second horse if diagnosed., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Background: Plasma α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropin (ACTH) concentrations in horses vary with season, confounding diagnostic testing for pituitary pars intermedia dysfunction (PPID)., Hypothesis: The goals of this study were to determine whether seasonal variation in plasma α-MSH and ACTH concentrations in horses is influenced by geographic location, breed, or PPID., Animals: Healthy light breed horses residing in Florida, Massachusetts, and Finland (n = 12 per group); healthy Morgan horses (n = 13); healthy ponies (n = 9) and horses with PPID (n = 8)., Methods: Monthly plasma α-MSH and ACTH concentrations were measured by radioimmunoassay. Nonlinear regression analysis was used to estimate the time of peak hormone concentrations. Mean hormone concentrations in fall and nonfall months were compared., Results: The fall peak plasma α-MSH concentration occurred earlier in horses residing at more northern locations. Mean seasonal α-MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in horses living in more southern locations. Plasma ACTH but not α-MSH concentrations were higher in Morgan horses compared with light breed horses from the same location. Hormone concentrations of ponies did not differ from those of horses during either season. Concentrations of both hormones were high in the fall compared with the spring in horses with PPID., Conclusions and Clinical Importance: These findings suggest geographic location of residence and breed may affect the onset, amplitude, or both of the seasonal peak of pars intermedia (PI) hormones and should be considered when performing diagnostic testing for PPID. Horses with PPID maintain seasonal regulation of PI hormone output., (Copyright © 2011 by the American College of Veterinary Internal Medicine.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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)-alpha plasma concentration was determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF-alpha 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-gamma as well as PBMC TNF-alpha 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.

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 concentrations were influenced by season. The ACTH baseline concentrations and response to TRH were not correlated with results of the DST. Results of DST were abnormal only in clinically abnormal horses or those with pars intermedia hyperplasia, but were within reference range in 17 of 26 tests in these horses., Conclusions and Clinical Relevance: The ACTH response to TRH is a useful test for diagnosis of pituitary gland hyperplasia, particularly in horses in which baseline ACTH concentrations are within reference range. The DST was specific but not sensitive and was inconsistent for individuals, and results often did not agree with the TRH test response.

Parkinson's disease (PD) is a leading cause of neurologic disability in the aged population. Remarkable progress has been made in the past decade to understand the cellular and molecular events that occur in PD. However attempts to unravel the early, initiating factors in the pathogenesis of dopaminergic neurodegeneration and PD have been limited by the lack of a suitable animal model. Models in which there has been genetic or environmental manipulation are not of use in determining the natural cause of a disease. While a large scale prospective human study would be ideal, the relatively low prevalence of PD makes this approach economically and logistically infeasible. Equine pituitary pars intermedia dysfunction (PPID) is a spontaneous, progressive neuroendocrine disease that commonly affects aged horses and ponies. PPID results from neurodegeneration of the dopaminergic periventricular neurons that innervate the intermediate lobe of the pituitary. PPID is 10-20 times more prevalent than PD and may be readily diagnosed without a need for advanced imaging technology. Although the diseases are anatomically distinct, recent evidence suggests the pathogenesis of dopaminergic neuronal damage in PPID may have significant similarities to that of PD. In this review, the similarities and differences in the pathology of neurodegeneration in PPID and PD are compared. The potential utility of the horse as a model of spontaneous dopaminergic neurodegeneration is discussed.

Fifteen horses with pituitary pars intermedia dysfunction were studied. The horses were of various breeds and between 15 and 28 years of age. Control horses matched for breed and age were studied for comparison. Evaluations included complete blood cell count and serum biochemical analysis, electromyography, and gluteus medius muscle biopsies for histochemical, morphometric, and ultrastructural analysis. No differences were found between groups of horses on routine laboratory analysis or electromyography. We demonstrated that muscle wasting in diseased horses was the result of atrophy of types 2A and 2B muscle fibers and loss of type 2B myofibers. Mild non-specific non-inflammatory myopathic alterations such as myofiber size variation, internal nuclei, perimysial, endomysial and sarcoplasmic fat accumulation were observed. At the ultrastructural level, subsarcolemmal mitochondrial accumulation and increased lipid droplets were evident. Similar to other species, this study confirmed atrophy of type 2 fibers as the cause of muscle mass loss in horses with Cushing's disease.