Pituitary Pars Intermedia Dysfunction (PPID) is a condition in horses characterized by a dysfunction of the pituitary gland, specifically the pars intermedia. This dysfunction leads to an overproduction of certain hormones, notably adrenocorticotropic hormone (ACTH), which can affect various physiological processes. PPID is commonly diagnosed in older horses and is associated with clinical signs such as hirsutism, laminitis, and changes in body condition. The condition is also referred to as equine Cushing's disease. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, and management of Pituitary Pars Intermedia Dysfunction in equine populations.
Waitt Wolker LH, Black A, Lee JK.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 , 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...
Sundra T, Kelty E, Rossi G, Rendle D.Dopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. However, some horses are refractory to daily oral pergolide, the recommended registered treatment. Extended-release cabergoline (ERC) injection may offer an alternative. The objective of this retrospective case series was to describe clinical and endocrinological responses to ERC. Unassigned: Medical records of horses treated with weekly intramuscular injections of ERC (5 mg/mL, BOVA Aus) at either 0.01 mg/kg (high dose, HD) ( = 10) or 0.005 mg/kg (low dose, LD) ( = 30) w...
Ireland JL, Lester A, Banse HE.Measurement of basal adrenocorticotropic hormone (ACTH) concentration is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID). Although several pre-analytical and analytical factors have been reported to affect basal ACTH concentrations in equids, the extent to which these have been evaluated in the context of PPID diagnosis is unclear. The objectives of this scoping review were to identify and systematically chart current evidence about pre-analytical and analytical factors affecting basal ACTH concentrations in adult domestic equids. Systematic searches of ...
Clark BL, Norton EM, Bamford NJ, Randhawa IAS, Kemp KL, McCue ME, Bertin FR, Stewart AJ.Insulin dysregulation (ID) is central to equine metabolic syndrome. There are limited epidemiological studies investigating dynamic testing of ID in ponies. Objective: To evaluate prevalence and risk factors for ID through dynamic testing of hyperinsulinaemia (DHI) and insulin resistance (IR). Methods: Cross-sectional. Methods: Sex, age, breed, height, cresty neck score (CNS), body condition score (BCS), laminitis, HMGA2:c.83G>A genotype and pituitary pars intermedia dysfunction (PPID) status were documented. Dynamic hyperinsulinaemia was diagnosed with an oral sugar test (OST) and IR with an ...
Colbath AC, Fortin JS, Burglass CM, Panek C, Vergara-Hernandez FB, Johnson TN, Robison CA, Logan AA, Nelson NA, Nielsen BD, Schott HC.Pathological fractures have been reported in equids with pituitary pars intermedia dysfunction (PPID) but their prevalence and pathogenesis is unknown. Objective: 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. Methods: 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 g...
Drozdzewska K, Winter J, Barton AK, Merle R, Gehlen H.The basal (bACTH) and post-thyrotropin-releasing hormone stimulation concentration of adrenocorticotropin (pACTH) are recommended for diagnosis of pituitary pars intermedia dysfunction (PPID). Many factors influence bACTH (e.g., disease, age, month) and some affect the results only in autumn (e.g., breed, colour, sex). There are discrepancies about the impact of feeding on b/pACTH. Objective: To determine whether feeding, month, age, breed, colour, sex and body condition score affect b/pACTH. Methods: Prospective crossover. Methods: Sixty-one animals were divided into groups: healthy, PPID, tr...
Frers F, Delarocque J, Feige K, Huber K, Warnken T.The underlying molecular mechanisms leading to insulin dysregulation are poorly understood in horses. Therefore, this study aimed to determine if insulin dysregulation is associated with an altered basal expression and extent of phosphorylation of key proteins of the insulin signaling cascade in liver (LT), muscle (MT), and subcutaneous adipose tissue (AT) under basal and stimulated conditions. Twelve Icelandic horses were subjected (1) to an oral glucose (Gluc PO) challenge and (2) to an intravenous (Ins IV) insulin challenge in a crossover study. Biopsies of LT, MT, and AT were taken in vivo...
Stewart AJ, Ireland JL, Durham AE, McGowan CM.Equine pituitary pars intermedia dysfunction (PPID) is common in aged horses. The majority of horses respond well to treatment, but treatment is lifelong, meaning accurate diagnosis of PPID is important. Similar to any condition, there is no perfect laboratory test to diagnose PPID and accuracy is affected by the characteristics of the population in which the test is being evaluated. This review details the importance of consideration of clinical factors and diagnostic test accuracy. Basal adrenocorticotrophic hormone (ACTH) concentration is used most frequently in practice and has very good d...
Menzies-Gow NJ, Banse HE, Duff A, Hart N, Ireland JL, Knowles EJ, McFarlane D, Rendle D.Pituitary pars intermedia dysfunction (PPID) is a prevalent, age-related chronic disorder in equids. Diagnosis of PPID can be challenging because of its broad spectrum of clinical presentations and disparate published diagnostic criteria, and there are limited available treatment options. Objective: To develop evidence-based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature. Methods: Evidence-based clinical guideline using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Methods: Research questions ...
Adams AA, Siard-Altman MH, Reedy SE, Barker D, Elzinga S, Sanz MG, Urschel K, Ireland JL.Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation test has been recommended for diagnosis of early or mild cases. However, it is currently not recommended for year-round use due to marked seasonal variability. The aims of this cohort study were to evaluate effects of month and season on adrenocorticotropic hormone (ACTH) responses to TRH stimulation and to derive monthly cut-offs for PPID d...
de Laat MA, Sillence MN.Blood glucose concentration is often measured during an oral glucose test (OGT), but is not thought to aid in diagnosing insulin dysregulation (ID) or pituitary pars intermedia dysfunction (PPID). The aim of this retrospective study was to investigate whether the change in blood glucose concentration during an OGT aligned with indicators of equine metabolic syndrome or PPID, including serum insulin and plasma ACTH concentrations, clinical observations, age, sex, breed type and the test dose. The cohort included 149 horses, miniature horses, and ponies that had undergone an in-feed OGT and clin...
Vorster DM, Wang W, Kemp KL, Bamford NJ, Bertin FR.The thyrotropin-releasing hormone (TRH) stimulation test is used to diagnose pituitary pars intermedia dysfunction (PPID) using 10- or 30-min protocols. Imprecise sampling time for the 10-min protocol can lead to misdiagnoses. Objective: To determine the effect of imprecise sampling time for the 30-min protocol of the TRH stimulation test. Methods: In vivo experiment. Methods: Plasma immunoreactive adrenocorticotropin (ACTH) concentrations were measured 9, 10, 11, 29, 30 and 31 min after intravenous administration of 1 mg of TRH in 15 control and 12 PPID horses. Differences in ACTH concent...
Herbst AC, Coleman MC, Macon EL, Brokman A, Stromberg AJ, Harris PA, Adams AA.Information on the management and health of US senior horses (≥15 years of age) is currently limited. Objective: Provide information on (1) primary use of US senior horses, (2) reasons and risk factors for horse retirement, (3) exercise management, (4) prevalence of low muscle mass and (5) risk factors for, and owner-perceived consequences of, low muscle mass. Methods: Online survey. Methods: Survey responses from 2717 owners of U.S.-resident senior horses (≥15 years of age) were analysed descriptively and inferentially, using ordered and binomial logistic regression, ANOVA and the Kru...
McGowan CM, Ireland JL.Equine endocrine disease is an important area for equine research, requiring an appropriate case definition for inclusion and criteria for exclusion from disease. Defining a case for research may be different from criteria for clinical diagnosis. Further, clinical diagnosis recommendations have been changing regularly, making this area challenging for equine scientists. This review discusses the diagnosis of major equine endocrine diseases, pituitary pars intermedia dysfunction, equine metabolic syndrome and insulin dysregulation, focusing on the most appropriate diagnostic methods for researc...
Bamford NJ, Stewart AJ, El-Hage CM, Bertin FR, Bailey SR.Plasma adrenocorticotropic hormone (ACTH) concentration is commonly measured to diagnose pituitary pars intermedia dysfunction (PPID). Several intrinsic and extrinsic factors affect ACTH concentrations, including breed. The objective of this study was to prospectively compare plasma ACTH concentrations among different breeds of mature horses and ponies. Three breed groups comprised Thoroughbred horses (n = 127), Shetland ponies (n = 131) and ponies of non-Shetland breeds (n = 141). Enrolled animals did not show any signs of illness, lameness or clinical signs consistent with PPID. Blood ...
Kaneps AJ.Regenerative medicine therapies have become significant tools for treatment of joint, soft tissue, and a variety of other conditions in animals and humans. Regenerative medicine aims to restore form and function of injured tissues using the body's own resources such as cells, fluids (ie, plasma and serum), and their resulting anti-inflammatory and prohealing cytokines. Platelet-rich plasma and other hemoderivatives have application for joint disorders such as osteoarthritis, cartilage injury, synovitis, and soft tissue injuries. These therapies achieve anti-inflammatory and healing effects wit...
Zapf AM, Fey K, Büttner K, Gröf M, Staszyk C.Pituitary pars intermedia dysfunction (PPID) and dental disorders are of major concern in horses older than 15 years. Although PPID in geriatric horses and dental disorders in all age groups are well described, a connection between this endocrine disease and pathological changes in equine dental structures has not yet been investigated. In humans, periodontitis is considered to be a complication of systemic diseases like diabetes mellitus type 2, obesity and various conditions leading to an impaired immune response. In PPID, cross links to insulin and immune dysregulations are proven. The aim ...
Knowles EJ, Hyde C, Harris PA, Elliott J, Menzies-Gow NJ.A chemiluminescent immunoassay is commonly employed to measure adrenocorticotrophic hormone (ACTH) concentrations to assist pituitary pars intermedia dysfunction diagnosis. In a previous study, seasonally-dependent assay cross-reactivity to endogenous equine corticotropin-like intermediate lobe peptide (CLIP, ACTH 18-39) was suspected. The present study aimed to demonstrate binding of endogenous equine CLIP to the capture antibody of the ACTH chemiluminescent immunoassay. Liquid chromatography - mass spectrometry (LCMS) methods were optimised to identify selected ions from synthetic human ACTH...
Li FI, Spence RJ, de Laat MA, Harris PA, Sonntag J, Menzies-Gow NJ, Durham AE, Bailey SR, Sillence MN.High concentrations of adrenocorticotropic hormone (ACTH) are used as an indicator of pituitary pars intermedia dysfunction (PPID), but other factors that may influence ACTH need to be understood, if diagnostic reference ranges for ACTH are to be used with confidence. Insulin dysregulation (ID) could be one such factor, as insulin affects pituitary hormones in other species. Objective: To test the hypothesis that a relationship exists between high insulin and high ACTH in aged (>15-year-old) animals with no clinical signs of PPID. Methods: A cohort study. Methods: Thirteen horses and eleven p...
Xue C, Davis J, Berghaus LJ, Hanafi A, Vaughn SA, Hart KA.Donkeys with clinical signs of pituitary pars intermedia dysfunction are treated with oral pergolide mesylate despite the lack of species-specific pharmacokinetic data. Objective: To evaluate the pharmacokinetics of intragastric and oral pergolide mesylate in healthy donkeys (Equus asinus). Methods: Pharmacokinetic study. Methods: Six healthy donkeys were administered pergolide mesylate (Prascend®) at 2 μg/kg bodyweight (bwt) intragastrically once, then once daily per os (PO) for 5 days. Blood samples were collected at 0, 10, 20, 30 and 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and ...
Stoeckle SD, Timmermann D, Merle R, Gehlen H.Pituitary pars intermedia dysfunction is one of the most common diseases of aged horses and ponies. In Parkinson's disease, which is, similar to PPID, a disease that involves oxidative damage to dopaminergic pathways but with different clinical signs, alterations to the serum amino acid profile have been reported. To examine changes in the plasma amino acid profile in horses with PPID, EDTA plasma of horses that were presented for various reasons that required laboratory examinations of blood anticoagulated with EDTA was collected. With this plasma, the basal ACTH concentration as well as the ...
Kirkwood NC, Hughes KJ, Stewart AJ.Poor recognition of subtle clinical abnormalities and equivocal ACTH concentrations make early diagnosis of PPID difficult. Progressive clinical findings and corresponding ACTH concentrations in horses transitioning to PPID over time have not been documented. Seven horses with ACTH concentrations equivocal for PPID (utilizing locally derived, seasonally adjusted diagnostic-cut off values (DCOV)) and no clinical signs of PPID were selected. Sequential measurement of basal and thyrotropin-releasing hormone (TRH)-stimulated ACTH concentrations and recording of clinical findings occurred from Octo...
Kirkwood NC, Hughes KJ, Stewart AJ.Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing ...
Steel NL, Ireland JL, McGowan CM.In horses/ponies with pituitary pars intermedia dysfunction (PPID), pergolide mesylate treatment, with monitoring of therapeutic response, is recommended by contemporaneous literature and equine endocrinologists. However, it is unknown whether these recommendations are adhered to in private practice. This clinical audit aimed to compare treatment and monitoring of PPID cases in veterinary practice against available recommendations. Case data and basal plasma adrenocorticotropic hormone (ACTH) concentrations from all equids tested for PPID between 2012 and 2016 from a single veterinary practice...
Huang L, Palmieri C, Bertin FR.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 ...
Humphreys S, Kass PH, Magdesian KG, Goodrich E, Berryhill E.Elevated plasma adrenocorticotropic hormone (ACTH) is often used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. The hormone naturally increases in the fall in horses, and donkeys have been found to have higher ACTH concentrations than horses. However, circannual variation of ACTH has not been assessed in donkeys. The objective of the study was to establish seasonal variation of basal plasma ACTH concentrations over the course of a year in clinically healthy, non-geriatric donkeys. It was hypothesized that donkey ACTH concentrations would be higher than those reported in ho...
Kellon EM, Gustafson KM.Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglycemia...
Fisher D, Schliewert EC, Hooijberg EH.An endogenous adrenocorticotropic hormone (ACTH) concentration above the reference interval (RI) is commonly used as means for diagnosing equine pituitary pars intermedia dysfunction (PPID). Basal ACTH concentrations are highly dependent on photoperiod and RIs should be month- and location-specific. To date, no ACTH RIs have been specifically established for South Africa. This study aimed to determine geographically and seasonally relevant RIs for equine ACTH in the Gauteng province of South Africa. A longitudinal prospective study was conducted over twelve months to determine ACTH RIs for a r...
Durham AE, Potier JF, Huber L.Use of plasma adrenocorticotropic hormone (ACTH) concentrations for the diagnosis of PPID in equids requires awareness of other factors that might influence ACTH concentrations, including breed and time of year. This study was designed to investigate effects of breed on plasma ACTH concentrations and potential interactions between breed and time of year. Ten breeds were selected from a laboratory database containing data on plasma ACTH concentrations. Breeds represented were Arabians, Cobs, Connemara ponies, donkeys, Irish Sports horses, New Forest ponies, Shetland ponies, Thoroughbreds, Warmb...
Durham AE.Thyrotropin releasing hormone (TRH) stimulation testing is often used to support a diagnosis of pituitary pars intermedia dysfunction (PPID) in horses although it is unclear whether or not repeat TRH stimulation testing post-treatment is a valid means of assessing response to medical therapy. Laboratory submissions from 64 suspected equine PPID cases were examined including the initial pre-treatment TRH stimulation test and a follow up test within 100 days of starting medical therapy with pergolide. In a subset of cases, further follow-up tests were examined beyond 100 days of starting treatme...
Frank N, Elliott SB, Chameroy KA, Tóth F, Chumbler NS, McClamroch R.Pituitary pars intermedia dysfunction (PPID) is a risk factor for pasture-associated laminitis, which follows a seasonal pattern. Objective: Hormonal responses to season differ between PPID and unaffected horses. Methods: Seventeen horses aged 8-30 years (14 horses ≥ 20 years of age). Methods: Longitudinal observational study. Blood was collected monthly from August 2007 until July 2008 after pasture grazing and again after overnight stall confinement. Blood hormone and metabolite concentrations were measured and pasture grass samples were analyzed to determine carbohydrate content. Analysis...
Miller MA, Pardo ID, Jackson LP, Moore GE, Sojka JE.Functional evaluation of the pars intermedia (PI) is required for the early diagnosis of equine pituitary PI dysfunction (PPID), yet most assays target the hypothalamic-pituitary-adrenal axis, which regulates the pars anterior. In contrast, the PI is regulated by dopaminergic tone from hypothalamic neurons. Loss of dopaminergic inhibition is hypothesized to cause the PI hypertrophy and hyperplasia that result in the clinical manifestations of PPID. Domperidone, a dopamine receptor antagonist, should exacerbate the loss of dopaminergic inhibition in horses with PPID and increase the release of ...
Schreiber CM, Stewart AJ, Kwessi E, Behrend EN, Wright JC, Kemppainen RJ, Busch KA.To determine whether seasonal variations exist in endogenous plasma ACTH, plasma α-melanocyte-stimulating hormone (α-MSH), serum cortisol, and serum insulin concentrations and in the results of a dexamethasone suppression test for older, clinically normal geldings in Alabama. Methods: Cohort study. Methods: 15 healthy mixed-breed geldings (median age, 14 years). Methods: Sample collection was repeated monthly for 12 months. Dexamethasone (0.04 mg/kg [0.02 mg/lb], IM) was administered and cortisol concentrations were determined at 15 and 19 hours. Radioimmunoassays were used to measure ACTH, ...
Beech J, Boston R, Lindborg S.Changes in both adrenocorticotropin (ACTH) and cortisol concentration in response to thyrotropin releasing hormone (TRH) administration have been used to diagnose equine pituitary pars intermedia dysfunction (PPID), but the use of the 2 hormones has not been compared. Objective: Measuring ACTH concentration is superior to measuring cortisol concentration after TRH administration in differentiating between normal horses and those with PPID, and the 2 hormone concentrations are disassociated in PPID horses. Methods: Eleven horses and 2 ponies with PPID and 19 normal horses. Methods: A study eval...
Rohrbach BW, Stafford JR, Clermont RS, Reed SM, Schott HC, Andrews FM.Pituitary pars intermedia dysfunction (PPID) is common in older horses. Objective: To determine diagnosis frequency, prognostic factors, long-term survival, and owner satisfaction with treatment. Methods: 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 obtai...
Horn R, Stewart AJ, Jackson KV, Dryburgh EL, Medina-Torres CE, Bertin FR.Diagnosis of pituitary pars intermedia dysfunction (PPID) is problematic because of large variations in ACTH concentrations. Objective: Compare the test characteristics of baseline and post-thyrotropin-releasing hormone (TRH) stimulation plasma ACTH concentrations in horses using diagnostic cutoff values (DCOVs) and reference intervals (RIs) and determine the clinical consequences of using each method. Methods: One hundred six mature horses: 72 control cases and 34 PPID cases. Methods: Prospective case-controlled study. Horses underwent monthly TRH stimulation tests. Diagnostic cutoff values w...
Funk RA, Stewart AJ, Wooldridge AA, Kwessi E, Kemppainen RJ, Behrend EN, Zhong Q, Johnson AK.Results of diagnostic tests for equine pituitary pars intermedia dysfunction (PPID), including endogenous ACTH concentration and the overnight dexamethasone suppression test (DST), are affected by season. New and potentially more sensitive diagnostic tests for equine PPID, such as thyrotropin-releasing hormone (TRH)-stimulated ACTH response, have been developed, but have had limited evaluation of seasonality. Objective: Our purpose was to evaluate seasonal changes in plasma ACTH and alpha-melanocyte-stimulating hormone (α-MSH) responses to TRH administration. Methods: Nine, healthy, aged hors...
McFarlane D, Paradis MR, Zimmel D, Sykes B, Brorsen BW, Sanchez A, Vainio K.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). Objective: 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. Methods: 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 plas...
Haritou SJ, Zylstra R, Ralli C, Turner S, Tortonese DJ.Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing's disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing's disease and six matched controls. The nocturnal rises in p...
Jacob SI, Geor RJ, Weber PSD, Harris PA, McCue ME.Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a challenge as multiple factors (stress, exercise, and time of year) influence ACTH and cortisol concentrations. To assess endocrine status in a study designed to evaluate the effects of age and diet on glucose and insulin dynamics, we performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight dexamethasone suppression tests in March, May, August, and October on 16 healthy Thoroughbred and Standardbred mares and geldings. Horses were grouped by age: adult (mean ± SD; 8.8 ± 2.9 yr; n = 8) and aged (20...
Pollard D, Wylie CE, Newton JR, Verheyen KLP.Euthanasia is a complex topic, with animal owners using multiple factors to shape their decision-making process. Previous epidemiological studies have described causes of equine mortality in specific populations, but there is limited evidence regarding factors contributing specifically to equine euthanasia in Great Britain (GB). This observational study used a prospective cohort design: the objectives were to describe owner-reported reasons for euthanasia, estimate the rate of euthanasia and identify associated factors in horses/ponies enrolled in a web-based epidemiological study of laminitis...
McFarlane D, Holbrook TC.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. Objective: 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. Method...
Diez de Castro E, Lopez I, Cortes B, Pineda C, Garfia B, Aguilera-Tejero E.Equine pituitary pars intermedia function can be assessed by the measurement of baseline and thyrotropin releasing hormone (TRH)-induced concentrations of adrenocorticotropic hormone (ACTH); however, these measurements may be affected by the environment. Therefore, a prospective observational study evaluated the influence of feeding, time of the day, and season on baseline and TRH-induced concentrations of ACTH in healthy horses. Baseline ACTH was measured in 50 horses before and 2 h after feeding. Six research horses were subjected to a crossover study in which 6 TRH tests were performed in ...
Fortin JS, Hetak AA, Duggan KE, Burglass CM, Penticoff HB, Schott HC.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...
Durham AE, Clarke BR, Potier JFN, Hammarstrand R, Malone GL.Pituitary pars intermedia dysfunction (PPID) is commonly investigated using plasma ACTH concentrations but problems exist with currently available diagnostic thresholds. Objective: To derive temporally specific diagnostic thresholds for equine plasma ACTH concentration to be used alongside clinical judgement in each individual week of the year and appropriate for the degree of clinical suspicion in any given case. Furthermore, to apply these thresholds to compare the prevalence of high and low ACTH in two subgroups of animals with high and low clinical suspicion of PPID. Methods: A retrospecti...
Firshman AM, Valberg SJ.Insulin resistance is thought to be involved in the pathogenesis of many equine conditions such as pars intermedia dysfunction, equine metabolic syndrome, diabetes mellitus, hyperlipaemia, laminitis, endotoxaemia and osteochondrosis dissecans (OCD); whereas polysaccharide storage myopathy in Quarter Horses and equine motor neuron disease (EMD) have been associated with increased insulin sensitivity. However, it is clear that there is not one ideal test, in terms of both practicality and accuracy, for evaluating insulin sensitivity in horses and improved diagnostic techniques are required. This...
Miller AB, Loynachan AT, Bush HM, Hart KA, Barker VD, Campana-Emard AG, Grubbs ST, Adams AA.It remains unclear how pituitary pars intermedia dysfunction (PPID) and pergolide treatment (Prascend [pergolide tablets]) affect endocrine and immune function in horses. To evaluate these effects, blood was collected regularly from 28 university-owned horses (10 Non-PPID, 9 PPID control [PC], and 9 PPID treatment [PT]) over approximately 15 mo. Pergolide treatment was initiated after Day 0 collections. Analyses included ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in vitro stimulat...
Frank N, Andrews FM, Sommardahl CS, Eiler H, Rohrbach BW, Donnell RL.A combined dexamethasone (DEX) suppression/thyrotropin-releasing hormone (TRH) test (DEX/TRH test) has been developed to evaluate horses for presence of a pars intermedia pituitary adenoma (PIPA), but to the authors' knowledge, the accuracy of this test has not been previously determined. Objective: The sensitivity and specificity of the DEX/TRH test can be determined by comparing test results with histopathologic examination findings. Methods: Age of 42 horses of various breeds ranged from 2 to 33 years. Methods: Plasma cortisol concentration was measured before and 24 hours after IV administ...
Donaldson MT, Jorgensen AJ, Beech J.To determine prevalence and clinical features of pituitary pars intermedia dysfunction (PPID) in horses with laminitis. Methods: Case series. Methods: 40 horses with laminitis. Methods: 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, t...
McFarlane D, Beech J, Cribb A.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 observ...
Mendoza FJ, Toribio RE, Perez-Ecija A.The donkey evolved under harsh and arid environmental conditions, developing unique energy-efficiency traits, with an efficiency to rapidly mobilize fat in situations of increased energy demands or when food is scarce. This evolution has led to an inherent predisposition of donkeys to obesity, dyslipidemias, insulin dysregulation/metabolic syndrome, pituitary pars intermedia dysfunction, and endocrinopathic laminitis. Marked differences have been described in hormone dynamics and testing protocols for the diagnosis of these endocrine and metabolic diseases in donkeys compared with horses, unde...
Love S.In the horse, adenomata of the pairs intermedia of the pituitary gland have been associated with the distinct clinical entity of Cushing's disease which arises largely as a result of excessive secretion of adrenocorticotropin (ACTH) or other proopiomelanocortin (POMC) peptides. Pars intermedia peptide secretion is under dopaminergic control and compounds such as pergolide or bromocriptine, which are dopamine agonists, can palliate the clinical signs. A variety of endocrinological abnormalities, relevant to both pathogenesis and diagnosis, may be demonstrated in equine Cushing's disease, includ...
Gehlen H, Schwarz B, Bartmann C, Gernhardt J, Stöckle SD.Appropriate medical care for donkeys is challenging despite being important working animals in non-industrialized countries and pets in first world countries. Although the same principles of diagnosis and therapy as in horses are commonly applied, there are differences in reference values and physiologic reaction to dynamic tests. However, donkeys seem to suffer from typical equine diseases, such as metabolic syndrome and pituitary pars intermedia dysfunction (PPID). Asinine metabolic syndrome (AMS) comprises obesity, insulin dysregulation, and laminitis. The principles of diagnosis are simila...
Tatum RC, McGowan CM, Ireland JL.Pergolide, a dopamine agonist, is commonly administered to manage pituitary pars intermedia dysfunction (PPID), a progressive neurodegenerative disease prevalent in aged horses. However, available evidence regarding pergolide's efficacy in improving clinical and endocrine parameters is limited. The aim of this systematic review was to assess published literature and evaluate evidence regarding whether pergolide treatment results in improvement of clinical signs and/or adrenocorticotrophic hormone (ACTH) concentration compared to no treatment or other unlicensed treatments. Systematic searches ...
Hu K, Stewart AJ, Yuen KY, Hinrichsen S, Dryburgh EL, Bertin FR.Determination of plasma adrenocotrophic hormone (ACTH) concentration (endogenous or thyrotropin-releasing hormone [TRH] stimulation test) is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID) in horses. Because ACTH is unstable, samples often are frozen to be shipped to laboratories or to allow for batch analysis of research samples. However, the effect of multiple freeze-thaw cycles on equine ACTH is unknown. Objective: To determine the effects of multiple freeze-thaw cycles on immunoreactive ACTH concentration. Methods: Twenty-eight horses ranging from 10...
McFarlane D.Despite there being only 2 common endocrine diseases in horses, pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS), diagnosis is still confusing. Failing to consider horse factors and treating based on laboratory results only have caused many animals to receive lifelong drug treatment unnecessarily. Increased plasma ACTH, baseline or TRH stimulated, supports a diagnosis of PPID; however, breed, age, thriftiness, illness, coat color, geography, diet, and season also affect ACTH concentration. Insulin dysregulation, the hallmark of EMS, can result from insulin resis...
Durham AE.Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal d...
Kirkwood NC, Hughes KJ, Stewart AJ.Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing ...
Horn R, Bertin FR.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). Objective: To investigate the diagnostic value of combining the TRH stimulation test and the 2-step insulin sensitivity test to diagnose PPID and ID simultaneously. Methods: 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...
