Dermatitis, cellulitis, and osteomyelitis caused by Aspergillus nidulans in a horse with pituitary pars intermedia dysfunction.

Clinical and histologic examination of a 12-y-old client-owned Quarter Horse gelding with pituitary pars intermedia dysfunction revealed dermatitis, cellulitis, and osteomyelitis caused by Aspergillus nidulans, confirmed by a PCR assay. This novel presentation of a fungal disease in a horse was characterized by aggressive local invasion and failure to respond to all medical therapy attempted over a 1-y period. Treatments included systemic and topical antifungals, anti-inflammatories, and use of cellular matrices. Surgical excision was not attempted but should be strongly considered early in the disease process in similar cases if clean margins can be achieved. Postmortem findings were of locally aggressive disease with no dissemination.

Lumbar vertebral bone density is decreased in horses with pituitary pars intermedia dysfunction.

BACKGROUND: Pathological fractures have been reported in equids with pituitary pars intermedia dysfunction (PPID) but their prevalence and pathogenesis is unknown. OBJECTIVES: To compare: (1) bone mineral density (BMD) in weight bearing and nonweight bearing bones in PPID+ equids and aged and young PPID- controls; and (2) biomechanical properties of the fourth lumbar vertebral body in PPID+ equids and aged PPID- equids. STUDY DESIGN: Case-control study: five PPID+ equids and six aged and four young PPID- control horses. METHODS: PPID status was based on clinical signs and necropsy examination of the pituitary gland (PG). The lumbar vertebral column, right front third metacarpus (MC3), left hind third metatarsus (MT3), and PG were removed after euthanasia. BMD was determined by quantitative computed tomography of regions of interest (ROI) in each bone and biomechanical testing was performed on the fourth lumbar vertebral body. Serum concentrations of parathormone (PTH), ionised Ca++ , 25-hydroxyvitamin D, and osteocalcin (OC) were also measured. Data were analysed using one-way ANOVA and correlation analyses. RESULTS: BMD of trabecular and cortical regions of interest (ROI) of the third, fourth (L4), and fifth lumbar vertebrae were significantly lower in PPID+ equids as compared with aged (p < 0. 001) and young (p < 0.01) PPID- controls. In contrast, no differences were found in BMD of trabecular or cortical ROIs of MC3 and MT3 between groups. No differences were detected in force at fracture, displacement at fracture, Young's modulus or strain of L4 between PPID+ and aged PPID- horses. No differences were found in serum PTH, ionised Ca++ , 25-hydroxyvitamin D, or OC concentrations between groups. MAIN LIMITATIONS: Limited number of equids studied and variation in test results. CONCLUSIONS: BMD of nonweight bearing bones can be decreased with PPID and could increase risk of developing pathological fractures.

Correlation of pituitary histomorphometry with dopamine and dopamine D2 receptor expression in horses with pituitary pars intermedia dysfunction.

Pituitary pars intermedia dysfunction (PPID) is an endocrinopathy commonly affecting old horses. It is a spontaneously occurring, progressive disease that is still poorly understood. Previous studies have observed neurodegeneration of the dopaminergic inhibition of melanotrophs, which leads to decreased dopamine (DA) in the pars intermedia (PI) and increased pro-opiomelanocortin-derived peptides circulating in plasma. However, rats knockout for the dopamine D2 receptor (D2r) similarly develop PI hypertrophy and hyperplasia. Thus, based on the current pathophysiological theory of PPID, whether the decreased DA or the D2r dysfunction leads to PPID is still unclear. To test this, a total of 28 retrospective cases of horses with PPID were collected, graded and the expression of tyrosine hydroxylase (TH) and D2r in the PI were determined. The histological and immunohistochemical results demonstrated that horses with higher tumor histological grades had reduced TH expression with increased D2r immunoreactivity colocalized in the PI (p < 0.001, p < 0.05 respectively). This correlation supports the role of DA in the pathogenesis of continuous unregulated proliferation of neoplastic cells in PI and indicates the efficiency of D2r agonists as a treatment for PPID.

Development and Evaluation of a Muscle Atrophy Scoring System (MASS) for Horses.

Loss of skeletal muscle mass likely compromises performance and welfare in horses and thus routine monitoring would be valuable. Currently available methods to assess muscle mass require expert knowledge and are often expensive. To provide a simple method, a muscle atrophy scoring system (MASS) was created and tested by three evaluators (raters) in 38 horses of varying age, breed, and health status. Inter-rater agreement on atrophy scores was in the good-to-excellent range for ratings of the neck (ICC = 0.62), back (ICC = 0.62) and hind (ICC = 0.76) regions but was poor for the abdominal region (ICC = 0.29). Due to this low agreement, the abdominal region was excluded from further analysis. Associations between muscle atrophy scores and age, pituitary pars intermedia dysfunction (PPID) status, and body composition indicators, including weight and estimated fat-free mass (FFM), were examined. Weight was inversely associated with neck, back and hind muscle atrophy scores (ß = -0.008, ß = -0.008, ß = -0.009, respectively; all P <0.001), but estimated FFM was not associated with muscle atrophy scores at any region (P >0.05). Age was positively related to neck (ß = 0.030, P <0.01), back (ß = 0.037, P <0.001) and hind (ß = 0.040, P <0.001) muscle atrophy scores. PPID-positive horses (n = 4) had higher muscle atrophy scores than PPID-negative horses (n = 23), even after adjusting for age (P <0.05). This data suggests that neck, back and hind region evaluations by individual raters likely have acceptable reliability. In addition, these findings support further evaluation of the potential benefits of the MASS to identify and monitor muscle atrophy in horses.

Preliminary study on the effects of pergolide on left ventricular function in the horses with pituitary pars intermedia dysfunction.

BACKGROUND: Pituitary pars intermedia dysfunction (PPID), a neurodegenerative disease leading to reduced dopamine production, is a common disease in aged horses. The treatment is based on administration of the dopamine agonist pergolide. This drug has been related to valvular fibrosis in humans, but the cardiovascular effect of this drug has not yet been investigated in horses. OBJECTIVES: To determine whether pergolide induces valvular disease in horses or affects the cardiac function. METHODS: Standard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in horses with diagnosed PPID based on adrenocorticotropic hormone dosage. Measurements taken in horses treated with pergolide were compared with those from untreated horses with nonparametric t-tests. Furthermore, measurements from follow-up examinations performed at least three months after the initial exam were compared with a Wilcoxon signed rank test for repeated measurements in each group. RESULTS: Twenty-three horses were included. None of the 12 horses under treatment developed valvular regurgitation. Furthermore, no differences in the measurements of the left ventricular systolic or diastolic function could be seen between the group of horses with treatment and those without treatment. Measurements taken in the follow-up exam did not differ compared to those taken in the initial exam in both groups. CONCLUSIONS: No changes of the left ventricular function assessed by TDE and STE could be shown in a small population of horses with confirmed PPID. Treatment with pergolide did not affect the ventricular function nor induce valvular disease.

Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy.

Equine pituitary pars intermedia dysfunction (PPID) is a common endocrine disease of aged horses that shows a similar pathophysiology as Parkinson's Disease (PD) with increased levels of α-synuclein (α-syn). While α-syn is thought to play a pathogenic role in horses with PPID, it is unclear if α-syn is also misfolded in the pars intermedia and could similarly promote self-aggregation and propagation. Consequently, α-syn was isolated from the pars intermedia from groups of healthy young and aged horses, and aged PPID-afflicted horses. Seeding experiments confirmed the prion-like properties of α-syn isolated from PPID-afflicted horses. Next, detection of α-syn fibrils in pars intermedia via transmission electron microscopy (TEM) was exclusive to PPID-afflicted horses. A bank of fragment peptides was designed to further characterize equine α-syn misfolding. Region 62-87 of equine and human α-syn peptides was found to be most prone to aggregation according to Tango bioinformatic program and kinetics of aggregation via a thioflavin T fluorescence assay. In both species, fragment peptide 62-87 is capable of generating mature fibrils as demonstrated by TEM. The combined animal, bioinformatic, and biophysical studies provide evidence that equine α-syn is misfolded in PPID horses.

Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction.

BACKGROUND: Pituitary pars intermedia dysfunction (PPID) develops slowly in aged horses as degeneration of hypothalamic dopaminergic neurons leads to proliferation of pars intermedia (PI) melanotropes through hyperplasia and adenoma formation. Dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity are markedly reduced in PI tissue of PPID-affected equids and treatment with the DA receptor agonist pergolide results in notable clinical improvement. Thus, we hypothesized that pergolide treatment of PPID-affected horses would result in greater DA and TH levels in PI tissue collected from PPID-affected horses versus untreated PPID-affected horses. To test this hypothesis, pituitary glands were removed from 18 horses: four untreated PPID-affected horses, four aged and four young horses without signs of PPID, and six PPID-affected horses that had been treated with pergolide at 2 µg/kg orally once daily for 6 months. DA concentrations and TH expression levels in PI tissues were determined by high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively. RESULTS: DA and TH levels were lowest in PI collected from untreated PPID-affected horses while levels in the pergolide treated horses were similar to those of aged horses without signs of PPID. CONCLUSIONS: These findings provide evidence of restoration of DA and TH levels following treatment with pergolide. Equine PPID is a potential animal model of dopaminergic neurodegeneration, which could provide insight into human neurodegenerative diseases.

Effects of advanced age and pituitary pars intermedia dysfunction on components of the acute phase reaction in horses.

Age, neurodegenerative disorders, and dysfunction of insulin secretion may be correlated with increased systemic concentrations of acute phase markers. Thus, the study aimed to determine the effect of age, pituitary pars intermedia dysfunction (PPID), and insulin dysregulation (ID) associated with PPID, on markers of the acute phase reaction. Twenty-nine mix-breed horses of both sexes were classified into groups: (1) healthy adult controls, (2) healthy non-PPID geriatric horses, (3) PPID ID+ horses, and (4) PPID ID- horses. Whole blood proinflammatory cytokine gene expression and serum concentrations of pro- and anti-inflammatory cytokines and acute phase proteins were measured. The data were analyzed using the Mann-Whitney U-test, and correlations between groups of data were assessed using Spearman's correlation coefficient. The tests were statistically significant if P < 0.05. No differences in the whole blood cytokine gene expression, serum cytokine concentrations, or acute phase proteins were noted between the groups. In the PPID ID group, there was a strong correlation between the ACTH concentration after the administration of thyrotropin-releasing hormone and the expression of IL-8 (r = 0.941; P = 0.0321). In the PPID ID+ group, there was a strong correlation between basal insulin concentrations and serum amyloid A (SAA; r = 0.936; P = 0.0083) as well as between postprandial insulin concentrations and SAA (r = 0.965; P = 0.001). These data suggest that neurodegeneration in horses moderately affects circulating markers of inflammation and that ID in horses with PPID influences acute phase inflammatory markers.

Relationships of inflamm-aging with circulating nutrient levels, body composition, age, and pituitary pars intermedia dysfunction in a senior horse population.

Similarly to aged humans, senior horses (≥20 years) exhibit chronic low-grade inflammation systemically, known as inflamm-aging. Inflamm-aging in the senior horse has been characterized by increased circulating inflammatory cytokines as well as increased inflammatory cytokine production by lymphocytes and monocytes in response to a mitogen. Little is currently known regarding underlying causes of inflamm-aging. However, senior horses are also known to present with muscle wasting and often the endocrinopathy pituitary pars intermedia dysfunction (PPID). Despite the concurrence of these phenomena, the relationships inflamm-aging may have with measures of body composition and pituitary function in the horse remain unknown. Furthermore, nutrition has been a focus of research in an attempt to promote health span as well as life span in senior horses, with some nutrients, such as omega-3 fatty acids, having known anti-inflammatory effects. Thus, an exploratory study of a population of n = 42 similarly-managed senior horses was conducted to determine relationships between inflamm-aging and measures of circulating nutrients, body composition, age, and PPID. Serum was collected to determine vitamin, mineral, and fatty acid content. Peripheral blood mononuclear cells were also isolated to determine inflammatory cytokine production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following stimulation with a mitogen, as well as to determine gene expression of interleukin(IL)-1ß, IL-6, IL-10, IFN-γ, and TNF-α. Serum IL-6 and C-reactive protein were determined by enzyme-linked immunosorbent assay. Whole blood was collected for hematological and biochemical analysis. Body composition was evaluated via ultrasound and muscle scoring for all 42 horses as well as by deuterium oxide dilution for a subset of n = 10 horses. Pituitary function was evaluated by measuring basal adrenocorticotropin hormone concentrations as well as by thyrotropin releasing hormone stimulation testing (to determine PPID status). Results showed various relationships between inflammatory markers and the other variables measured. Most notably, docosadienoic acid (C22:2n6c), docosapentaenoic acid (C22:5n3c), and folate were positively associated with numerous inflammatory parameters (P ≤ 0.05). Although no relationships were found between inflamm-aging and PPID, being positive for PPID was negatively associated with vitamin B12 (P ≤ 0.01). No relationships between inflammation and body composition were found. Even within this senior horse population, age was associated with multiple parameters, particularly with numerous inflammatory cytokines and fatty acids. In summary, inflamm-aging exhibited relationships with various other parameters examined, particularly with certain fatty acids. This exploratory study provides insights into physiological changes associated with inflamm-aging in the senior horse.

Evaluation of combined testing to simultaneously diagnose pituitary pars intermedia dysfunction and insulin dysregulation in horses.

BACKGROUND: The thyrotropin-releasing hormone (TRH) stimulation test and the 2-step insulin sensitivity test are commonly used methods to diagnose, respectively, pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID). OBJECTIVES: To investigate the diagnostic value of combining the TRH stimulation test and the 2-step insulin sensitivity test to diagnose PPID and ID simultaneously. ANIMALS: Twenty-seven adult horses, 10 control horses without PPID or ID, 5 horses with PPID only, 5 horses with ID only, and 7 horses with PPID and ID. METHODS: Randomized prospective study. Horses underwent a TRH stimulation test alone, a 2-step insulin sensitivity test alone, and combined testing with simultaneous TRH and insulin injection in the same syringe. Data were compared by 2-way repeated measures analysis of variance and 2 1-sided tests to demonstrate equivalence. Bland-Altman plots were generated to visualize agreement between combined and independent testing. RESULTS: The effect of combined testing on plasma adrenocorticotropic hormone, blood glucose concentration, or percentage decrease in blood glucose concentration was not significantly different from the effect obtained with independent testing. One control horse appeared falsely positive for PPID, 2 PPID-only horses appeared falsely positive for ID, and 1 PPID and ID horse appeared falsely negative for ID when tests were performed simultaneously. Bland-Altman plots supported the agreement between combined and independent testing. CONCLUSIONS AND CLINICAL IMPORTANCE: Combining the TRH stimulation test and the 2-step insulin sensitivity test appears to be a useful diagnostic tool for equine practitioners in the field, allowing testing of a horse for both PPID and ID simultaneously.

Effect of delayed plasma centrifugation on equine adrenocorticotropic hormone concentration.

Plasma adrenocorticotropic hormone (ACTH) concentration is used in the diagnosis of pituitary pars intermedia dysfunction (PPID) in horses. We enrolled 10 horses, 5 PPID-positive and 5 PPID-negative, in our study, September 20-22, 2016. On day 0, 5 mL of whole blood was collected into each of 6 EDTA tubes and immediately placed in a refrigerator at 7°C. One tube was centrifuged within 15 min of collection, followed by centrifugation of one tube from each horse at 4, 8, 12, 24, and 36 h following collection. At each time, centrifuged plasma was pipetted into 1.5-mL polypropylene tubes and stored at -80°C. None of the plasma samples were turbid, hemolyzed, or icteric. Plasma was shipped frozen with cold packs overnight to the Animal Health Diagnostic Center of Cornell University (Ithaca, NY) for analysis. The percent change from baseline (PCFB) was reported to standardize the data given that baseline values differed. The mean PCFB was 2.8 (95% confidence interval: -2.9%, 7.0%). Neither refrigeration of whole blood for up to 36 h prior to centrifugation nor freezing affected plasma ACTH concentrations significantly.

Evaluation of dynamic testing for pituitary pars intermedia dysfunction diagnosis in donkeys.

BACKGROUND: Endocrine disorders are common in donkeys. Pituitary pars intermedia dysfunction (PPID) is thought to be a frequent disturbance in donkeys due to their longevity. However, information on PPID dynamic testing in donkeys is lacking. OBJECTIVES: The objective of this study was to evaluate the previously described guidelines for PPID diagnosis in horses in donkeys with suspicion of PPID. STUDY DESIGN: Prospective experimental study. METHODS: Eighty donkeys were evaluated for PPID suspicion based on clinical signs and baseline adrenocorticotropic hormone (ACTH) concentrations. Six mix-breed donkeys (one jack and five non-pregnant jennies) fulfilling inclusion criteria were subjected to dexamethasone suppression test (DST), thyrotropin-releasing hormone stimulation test (TRH) and combined DST-TRH challenge. Tests were interpreted according to guidelines for PPID diagnosis in horses. RESULTS: Donkeys fulfilling inclusion criteria were diagnosed with PPID by TRH stimulation test (six of six). Both DST (three of six) and DST-TRH (4/6) challenges failed to detect those animals and showed conflicting results. Similarly, cortisol basal concentrations were not consistent with PPID suspicion. MAIN LIMITATIONS: Characterisation of seasonal and geographical location effect on baseline ACTH concentrations and response to TRH is compelling in this species. Further studies with a larger number of donkeys are needed. CONCLUSIONS: This is the first study in donkeys to evaluate common dynamic tests used for PPID diagnosis in horses. Preliminary results agree with the guidelines for PPID diagnosis in horses and baseline ACTH measurement followed by TRH challenge are recommended tests for diagnosis of PPID in donkeys.

Factors associated with survival, laminitis and insulin dysregulation in horses diagnosed with equine pituitary pars intermedia dysfunction.

BACKGROUND: Pituitary pars intermedia dysfunction (PPID) is a commonly described endocrine disorder in higher latitudes of the Northern hemisphere but the description of the disease at lower latitudes and in the Southern hemisphere is limited. OBJECTIVES: Document the clinical features of PPID at different Australian latitudes and climates, and investigate factors associated with survival, laminitis and insulin dysregulation (ID). STUDY DESIGN: Retrospective study of 274 equids from eight institutions across Australia. METHODS: A diagnosis of PPID was based on endogenous ACTH, overnight dexamethasone suppression test, thyrotropin-releasing hormone stimulation test or necropsy. Clinical and clinicopathologic characteristics of PPID and therapeutic responses were investigated. Laminitis was diagnosed by radiographic or histologic changes and ID was diagnosed based on endogenous insulin, an oral glucose test or a 2-step insulin-response test. RESULTS: Being a pony, having a higher body condition score and pergolide administration were associated with survival. The clinical presentation of PPID changed with latitude and climate, with anhidrosis and polyuria/polydipsia more commonly recognised at lower latitudes. Laminitis was diagnosed in 89.9% of cases and ID was present in 76.5% of cases in which they were investigated. MAIN LIMITATIONS: Despite the sample size, the lack of uniform testing at all locations (primary or referral cases) and the incompleteness of data sets limited the power of the statistical analyses. CONCLUSIONS: PPID can present with variable signs at different latitudes and climates, and ID should be investigated in equids diagnosed with PPID. Adequate body condition and administration of pergolide are fundamental in PPID management.

Endocrine Disorders of the Equine Athlete.

Equine athletes are affected by 2 major endocrine/metabolic disorders, insulin dysregulation (ID) and pituitary pars intermedia dysfunction. ID is a risk factor for laminitis in horses, which poses the greatest threat to performance because of the damage that it causes to hoof structures. This article includes an in-depth discussion of ID and other risk factors for laminitis that are grouped together as equine metabolic syndrome. As horses age, the risk of pituitary pars intermedia dysfunction increases, and this endocrine disorder may exacerbate preexisting ID and further increase the risk of laminitis.

PITUITARY PARS INTERMEDIA DYSFUNCTION (EQUINE CUSHING'S DISEASE) IN NONDOMESTIC EQUIDS AT MARWELL WILDLIFE: A CASE SERIES. ONE CHAPMAN'S ZEBRA ( EQUUS QUAGGA CHAPMANI) AND FIVE PRZEWALSKI's HORSES ( EQUUS FERUS PRZEWALSKII).

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.

Equine pituitary pars intermedia dysfunction: An international survey of veterinarians' approach to diagnosis, management, and estimated prevalence.

The objectives of the present study were to determine if diagnosis and treatment of equine pituitary pars intermedia dysfunction (PPID) vary by geographic region and to report the prevalence of PPID in horses as observed by veterinarians across locations. An online questionnaire was developed for veterinarians who treat horses. Veterinary associations, especially equine specialty subgroups, were contacted and a survey link was sent to members of each organization. Generalized linear models were used to examine whether the method of diagnosis and treatment of this condition, as well as its reported prevalence, differed by geographic region. Veterinarians from 426 separate clinics in 20 countries returned surveys. Diagnosis of PPID varied by region, but was usually based on clinical signs and an adjunct endocrine test. Horses with PPID were treated medically by 63% of veterinarians and 75% of these used pergolide mesylate as treatment. The median prevalence estimated was 1% and this did not differ by geographic location. Half the veterinarians were caring for 5 or more animals with PPID. Overall, diagnostic approach differed in geographic regions. In general, European veterinarians were more likely than those in North America to diagnose PPID based on clinical signs alone, without using an adjunct laboratory test. Veterinarians reported that cost and management responsibilities were their clients' primary concerns associated with the long-term treatment of this disease, which indicates a need for additional treatment options for PPID.

Les objectifs de la présente étude étaient de déterminer si le diagnostic et le traitement de la dysfonction de l'hypophyse médiale équine (DHME) varient selon la région géographique et signalent la prévalence de la DHME chez les chevaux, comme l'ont observé les vétérinaires dans différentes localisations. Un questionnaire en ligne a été développé pour les vétérinaires qui traitent les chevaux. Les associations vétérinaires, en particulier les sous-groupes de spécialités équines, ont été contactées et un lien pour un sondage a été envoyé aux membres de chaque organisation. Les modèles linéaires généralisés ont été utilisés pour examiner si la méthode de diagnostic et de traitement de cette condition, ainsi que sa prévalence déclarée, différaient selon la région géographique. Les vétérinaires provenant de 426 cliniques distinctes dans 20 pays ont répondu au sondage. Le diagnostic de DHME variait selon la région, mais était généralement basé sur les signes cliniques et un test endocrinien complémentaire. Les chevaux atteints de DHME ont été traités médicalement par 63 % des vétérinaires et 75 % de ceux-ci utilisaient le mésylate de pergolide comme traitement. La prévalence médiane estimée était de 1 % et cela ne différait pas selon la situation géographique. La moitié des vétérinaires prenaient soin de 5 animaux ou plus avec DHME. Dans l'ensemble, l'approche diagnostique différait selon les régions géographiques. En général, les vétérinaires européens étaient plus susceptibles que ceux en Amérique du Nord de diagnostiquer la DHME en se basant uniquement sur les signes cliniques, sans utiliser un test de laboratoire complémentaire. Les vétérinaires ont signalé que les coûts et les responsabilités en matière de gestion étaient les principales préoccupations de leurs clients liées au traitement à long terme de cette maladie, ce qui indique un besoin d'options de traitement supplémentaires pour DHME.(Traduit par Docteur Serge Messier).

Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction.

The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend® ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half-life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once-daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.

What's New in Old Horses? Postmortem Diagnoses in Mature and Aged Equids.

Postmortem findings in 241 equids admitted to a teaching hospital that were at least 15 years old at autopsy were reviewed (1) to determine disease prevalence, (2) to compare the cause of death (or euthanasia) in equids 15 to 19 years of age (n = 116) with that in equids ≥20 years of age (n = 125), and (3) to catalog coexisting lesions in equids with pituitary pars intermedia dysfunction (PPID). Breed and sex were evenly distributed between the age groups. Death or euthanasia was attributed to disease of the digestive system (41.5%), pituitary gland (12.9%), locomotor system (10.0%), nervous system (7.9%), cardiovascular system (4.6%), urinary system (4.6%), reproductive system (4.2%), respiratory system (4.2%), integumentary system (4.2%), lymphoid system (2.5%), liver (2.5%), or systemic neoplasia (1.2%). Nervous system disease was more common in the 15- to 19-year group; urinary tract disease was more common in the ≥20-year group. Neoplastic disease, regardless of systemic location, was the basis for death or euthanasia in 18.7% of all equids. Squamous cell carcinoma, lymphoma, and melanoma were the most common malignant neoplasms. PPID was the most common specific diagnosis, based on the postmortem presence of hyperplasia or adenoma, and was the reason for euthanasia in 47.7% of 65 equids with PPID. The most common nonpituitary causes for death or euthanasia in equids with PPID were colic, lameness, cancer, and spinal cord disease. Coexisting conditions in equids with PPID that were not considered the basis for euthanasia included neoplasms, infections, lameness, and recurrent airway obstruction.

Lamellar pathology in horses with pituitary pars intermedia dysfunction.

REASONS FOR PERFORMING STUDY: Hoof lamellar pathology in horses with pituitary pars intermedia dysfunction (PPID) has not been described previously. OBJECTIVES: To describe the histomorphometry and pathological lesions in hoof lamellar tissue of animals that had PPID with or without concurrent laminitis, with reference to age-matched controls. We hypothesised that lamellar lesions consistent with laminitis would be associated with PPID, even in animals without current or historical laminitis. STUDY DESIGN: Prospective case-control study. METHODS: Mid-dorsal hoof histological sections were obtained post mortem from the forelimbs of 16 PPID-affected animals either with (n = 6) or without laminitis (n = 10) and 10 age- and breed-matched controls. Sections were examined by a blinded veterinary pathologist. The length and width of 10 primary epidermal lamellae were measured using image analysis software. The morphology and pathology of primary and secondary epidermal lamellae were then typed or graded in axial, middle and abaxial regions. Fasting serum insulin, plasma adrenocorticotropin and blood glucose concentration were measured from blood samples taken prior to euthanasia. RESULTS: All animals with PPID and laminitis had fasting hyperinsulinaemia (median 74.1 miu/l, interquartile range 49.9-349.5 miu/l) whereas PPID animals without laminitis had serum insulin concentrations below the upper limit of the reference range (<20 miu/l). Lamellar pathology in PPID animals with laminitis was variable in severity and unrelated to the reported duration of laminitis (range 2 months-5 years). Most lesions were located abaxially within the lamellar tissue and included increased length and width of the lamellae, chronic abnormal keratinisation, interlamellar epidermal bridging and cell death with more acute lamellar tearing in some cases. The lamellae of PPID animals without laminitis were normal referent to the relevant control group. CONCLUSIONS: Whether PPID and hyperinsulinaemia have a causal inter-relationship or not, it may only be the hyperinsulinaemia that is associated with lamellar morphological alteration and pathology consistent with laminitis.

Perianesthetic development of diaphragmatic hernia in a horse with equine pituitary pars intermedia dysfunction (PPID).

A 21-year-old Thoroughbred gelding with a history of equine pituitary pars intermedia dysfunction (PPID) presented with priapism of 2 days' duration. The horse received a caudal morphine epidural and then underwent corpus cavernosum lavage and phallectomy under general anesthesia. The patient's recovery featured multiple unsuccessful attempts to stand and his respiratory distress persisted for several hours until he acutely developed severe colic and was euthanized. Necropsy findings revealed a pituitary adenoma of the pars intermedia, bilateral adrenal cortical hyperplasia, and diaphragmatic herniation. This report suggests that horses with PPID may present a greater risk for diaphragmatic hernia under general anesthesia or during procedures placing stress on the diaphragm, including anesthetic recovery.

Développement périanesthésique d'une hernie diaphragmatique chez un cheval atteint d'une dysfonction de l'hypophyse pituitaire (DHP). Un hongre Thoroughbred âgé de 21 ans avec une anamnèse de dysfonction de l'hypophyse pituitaire (DHP) a été présenté avec un priapisme présent depuis 2 jours. Le cheval a reçu une épidurale caudale de morphine et a ensuite subi un lavement du corps caverneux et une phallectomie sous anesthésie générale. Le rétablissement du patient a comporté de nombreuses tentatives infructueuses de se tenir debout et sa détresse respiratoire a persisté pendant plusieurs heures jusqu'à ce qu'il développe de graves coliques et soit euthanasié. Les constatations à la nécropsie ont révélé un adénome pituitaire de l'hypophyse, de l'hyperplasie corticale bilatérale et une herniation diaphragmatique. Ce rapport suggère que les chevaux atteints de DHP peuvent présenter un plus grand risque d'hernie diaphragmatique sous anesthésie générale ou durant des interventions exerçant un stress sur le diaphragme, y compris le réveil après l'anesthésie.(Traduit par Isabelle Vallières).