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.
Thane K, Uricchio C, Frank N.Diagnosis of pituitary pars intermedia dysfunction (PPID) using the thyrotropin-releasing hormone (TRH) stimulation test requires blood collection 10 minutes after TRH injection; it is unknown if small differences in timing affect test results. Objective: To determine whether early or late sampling results in a significant (≥10%) difference in plasma adrenocorticotropic hormone (ACTH) concentration compared to standard 10-minute sampling. Methods: Twenty-four healthy adult horses with unknown PPID status. Methods: In this prospective study, subjects underwent a single TRH stimulation test, ...
van Proosdij R, Frietman S.Geriatric horses (>15 years) represent a substantial proportion of the equine population. The objective of this study was to (1) report on the cause of death in geriatric horses on a single retirement centre, (2) to evaluate the relationship between PPID status, and mortality rate. Data of 194 horses was collected over an eight-year period. This providing data for 80 geriatric cases of mortality. The average age of horses that died was 26.2 years (±4.8 years). The majority (95%) of mortalities were euthanised, most frequently due to colic (20%), old age (19%), and lameness (15%). Overall m...
Grenager NS.Endocrinopathic laminitis (EL) primarily occurs because of insulin dysregulation (ID) mediated through downstream effects of insulin on IGF-1R in lamellar tissues. There is likely contributing vascular and metabolic dysfunction within the lamellae, but EL is relatively non-inflammatory. EL is associated with lamellar stretching, proliferation, and failure, ultimately causing failure of the suspensory apparatus of the distal phalanx. Proper education regarding mitigating risk factors makes this a largely preventable cause of laminitis. Annual hoof evaluation plus screening geriatric horses for ...
Kam YN, McKenzie K, Coyle M, Bertin FR.Pituitary pars intermedia dysfunction (PPID) is a common endocrinopathy of horses diagnosed with a thyrotropin-releasing hormone (TRH) stimulation test. Objective: Describe the repeatability of TRH stimulation in horses with and without PPID in winter and autumn. Methods: Twenty adult horses; 6 controls and 6 with PPID tested in autumn, 8 controls and 6 with PPID tested in winter with 3 controls and 3 with PPID tested in both seasons. Methods: Thyrotropin-releasing hormone stimulation was performed on 2 consecutive occasions, 1 week before and 1 week after the winter solstice and the autumn ...
Meyer JC, Hunyadi LM, Ordóñez-Mena JM.Accuracy of baseline ACTH for the diagnosis of PPID in horses varies between studies. Objective: To estimate the diagnostic accuracy of ACTH as a biomarker for PPID in adult horses and appraise potential causes of heterogeneity. Methods: Systematic review and meta-analysis. Methods: A literature review identified studies reporting diagnostic accuracy data for extraction. Risk of bias was evaluated using QUADAS-2. Two random-effects models, the hierarchical summary receiver operating curve (HSROC) and the bivariate binomial normal model (BBN) were used to pool accuracy measurements. We performe...
Gehlen H, Fisch J, Merle R, Trachsel DS.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. Objective: 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 hor...
Herbst AC, Johnson MG, Gammons H, Reedy SE, Urschel KL, Harris PA, Adams AA.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...
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...
Miller AB, Murphy BA, Adams AA.Blue light therapy can be used in horses to alter the natural photoperiod and inhibit winter hair coat growth. Seasonal increases in ACTH occur in the fall season but are exaggerated in horses with pituitary pars intermedia dysfunction (PPID). Additionally, PPID horses frequently present with hypertrichosis. Thus, blue light therapy was proposed as a potential management tool for hypertrichosis and for investigating the impact of photoperiod manipulation on ACTH. Eighteen PPID horses, aged 18 to 31 yr, from a university-owned research herd were selected and assigned to either the control group...
Tsuchiya T, Noda R, Ikeda H, Maeda M, Sato F.Pituitary pars intermedia dysfunction (PPID) is an endocrine disorder the clinical signs of which include infertility, but few reports have examined the relationship between PPID and reproductive performance in broodmares. Objective: Broodmares with infertility of unknown etiology were screened for PPID using baseline endogenous plasma ACTH concentrations, and its relationship with subsequent reproductive performance was analyzed. Methods: Sixty-seven Thoroughbred broodmares. Methods: Adrenocorticotropic hormone concentrations were measured in autumn. The broodmares were divided into 3 groups ...
Tatum RC, McGowan CM, Ireland JL.Measurement of basal adrenocorticotrophic hormone (ACTH) is currently used to diagnose pituitary pars intermedia dysfunction (PPID) in horses, yet a systematic review of the evidence for its use has not been undertaken. This study aimed to systematically review evidence regarding the sensitivity and specificity of the basal ACTH diagnostic test. Electronic databases were systematically searched in January 2019, September 2020 and January 2021, for English language publications published prior to these dates. Screening, data extraction and quality assessment of publications was undertaken by th...
Hague N, Durham AE, Menzies-Gow NJ.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. 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) ...
Hicks GR, Fraser NS, Bertin FR.Although there are many hormonal changes associated with reproduction, the effects of ovulation and early pregnancy on adrenocorticotropic hormone (ACTH) and insulin concentrations are poorly described. We hypothesise that both ovulation and early pregnancy will alter ACTH and insulin concentrations in healthy mares. Eighteen mares showing no clinical signs suggestive of, or laboratory findings consistent with, pituitary pars intermedia dysfunction PPID and insulin dysregulation (ID) are enrolled. ACTH, cortisol, insulin and glucose concentrations are measured over their peri-ovulatory period,...
Banse HE, Whitehead AE, McFarlane D, Chelikani PK.Pituitary pars intermedia dysfunction (PPID) is a common endocrine disorder of aged horses, with muscle atrophy as one of the clinical signs. We sought to compare muscle mass and regulation of skeletal muscle proteolysis between horses with PPID and muscle atrophy to older horses without PPID, and to assess the impact of treatment with pergolide (dopaminergic agonist) on PPID horses. We hypothesized that PPID-associated muscle atrophy is a result of increased proteolysis, and that markers of muscle atrophy and proteolysis would improve over time with pergolide treatment. Markers of muscle atro...
Miller AB, Loynachan AT, Barker VD, Adams AA.In order to better understand the influence of age on innate immune function in horses, blood was collected from twelve adult horses (aged 10-16 years; mean: 13 years) and ten geriatric horses (aged 18-26 years; mean: 21.7 years) for analysis of plasma myeloperoxidase, complete blood counts, and cytokine and receptor expression in response to in vitro stimulation with heat-inactivated Rhodococcus equi, heat-inactivated Escherichia coli, and PMA/ionomycin. Gene expression was measured using RT-PCR for IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-12α, IL-13, IL-17α, TLR2, TLR4, and TNFα. Endocrine fu...
Delarocque J, Reiche DB, Meier AD, Warnken T, Feige K, Sillence MN.Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. The identification of other biomarkers could provide an alternative or adjunct diagnostic method, to allow early intervention before laminitis develops. The present study characterised the metabolome of ponies with varying degrees of ID using basal and postprandial plasma samples obtained during a previous study, which examined the predictive power of blood insulin levels for the development of laminitis, in ponies fed a high-sugar diet...
Tatum RC, McGowan CM, Dean RS, Ireland JL.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 abou...
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...
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...
Christen G, Precht C, van der Kolk J, Fouché N, Gerber V.Endocrinopathic laminitis occurs as a consequence of hormonal derangements like pituitary pars intermedia dysfunction (PPID). The objective of the present study was to assess the occurrence of radiographic changes associated with chronic laminitis in elderly, clinically sound horses. Fifty-one horses were included in the study. Horses were assigned to different age groups, in groups according to their BCS and CNS as well as to groups with different ACTH concentrations in order to assess their risk of chronic laminitis (reported as odds ratios (OR) and confidence intervals (CI)). Horses assigne...
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 ...
Bamford NJ, Harris PA, Bailey SR.To compare circannual plasma concentrations of adrenocorticotropic hormone (ACTH) and seasonal dexamethasone suppression test (DST) results between three different equine breed groups. Methods: Six Standardbred horses, six Andalusian horses and six mixed-breed ponies were followed over a 1-year period, during which time groups were managed identically. Blood samples were collected monthly (around the autumn equinox) or in every second month (other times of the year) for the determination of plasma ACTH concentrations using a chemiluminescent immunoassay. Overnight DSTs were performed quarterly...
Fortin JS, Benskey MJ, Lookingland KJ, Patterson JS, Howey EB, Goudreau JL, Schott HC.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 ...
Gehlen H, Jaburg N, Merle R, Winter J.The aim of the present study was to evaluate (i) the effects of different intensities and types of treated pain on the basal concentrations of adrenocorticotropic hormone (ACTH) and cortisol, and (ii) the thyrotropin-releasing hormone (TRH) stimulation test, to determine whether treated pain caused a marked increase of ACTH, which would lead to a false positive result in the diagnosis of pituitary pars intermedia dysfunction (PPID). Methods: Fifteen horses with treated low to moderate pain intensities were part of the study. They served as their own controls as soon as they were pain-free agai...
Oberhaus EL, Thompson DL, Kerrigan LE, Chapman AM.Stress or excitement is a concern when performing endocrine tests on fractious horses. Sedation may be a solution; however, perturbation of test results may preclude useful information. Thyrotropin-releasing hormone (TRH) is a known stimulator of prolactin, thyroid-stimulating hormone (TSH), melanocyte-stimulating hormone (MSH), and ACTH. Thyrotropin-releasing hormone-induced ACTH is a diagnostic tool for the assessment of endocrinopathies such as pituitary pars intermedia dysfunction. It is unknown if drugs commonly used for sedation alter endocrine responses. The objective of this study was ...
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...
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...
Norton E, McCue ME.A role for a genetic contribution to equine metabolic syndrome (EMS) and pars pituitary intermedia dysfunction (PPID) has been hypothesized. Heritability estimates of EMS biochemical measurements were consistent with moderately to highly heritable traits. Further, genome-wide association analyses have identified hundreds of regions of the genome contributing to EMS and candidate variants have been identified. The genetics of PPID has not yet been proven. Continued research for the specific genetic risk factors for both EMS and PPID is crucial for gaining a better understanding of the pathophys...
Żak A, Siwińska N, Chełmecka E, Bażanów B, Romuk E, Adams A, Niedźwiedź A, Stygar D.The study aims to assess the impact of age, pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID) in horses on selected oxidative stress markers. The study includes 32 horses, divided into three groups: "young" adult group (aged 8-16 years old) "geriatric" group (aged 18-24 years old) and the "PPID" group (aged 15-31 years old). The PPID group was further divided into two subgroups: PPID ID+ and PPID ID- based on presence or absence of ID. We measured serum antioxidant stress markers in all horses: total oxidant status (TOS), total antioxidant capacity (TAC), ceruloplasmi...
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...
Dybdal NO, Hargreaves KM, Madigan JE, Gribble DH, Kennedy PC, Stabenfeldt GH.Pituitary pars intermedia dysfunction is a slowly progressive disorder that afflicts most breeds of horses. Because it shares features with human Cushing disease, it has been referred to as equine Cushing disease. A variety of tests of pituitary-adrenocortical function were performed on horses with evidence of pituitary pars intermediate dysfunction, and results were compared with those in healthy control horses. Diurnal variations in plasma cortisol concentration were not statistically different between control horses and those with pituitary pars intermedia dysfunction. An ACTH stimulation (...
Irvine KL, Burt K, Hill AJ, Shaw S, Papasouliotis K.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. Objective: 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 horm...
de Laat MA, Sillence MN, Reiche DB.Equine endocrinopathic laminitis is common and can be associated with an underlying endocrinopathy, such as equine metabolic syndrome (EMS), pituitary pars intermedia dysfunction (PPID), pasture consumption, or any combination of these factors. Objective: The aim of the study was to improve the risk assessment capabilities of clinicians, and to inform management strategies, for acute endocrinopathic laminitis by prospectively examining the phenotypic, hormonal, and clinical characteristics of the disease in a large cohort. Methods: Privately owned horses and ponies (n = 301) of any age, se...
Innerå M, Petersen AD, Desjardins DR, Steficek BA, Rosser EJ, Schott HC.Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. Objective: The aim of this study was to compare hair follicle stages in PPID-affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID-affected horses after 6 months of treatment with pergolide mesylate with those of control horses. Methods: Eight PPID-affected horses and four normal, age-matched, control horses. Methods: Skin biopsies were collected from the neck and rump of PPID-affected...
McFarlane D, Cribb AE.To determine whether a deficiency in systemic or local (pars intermedia) antioxidant capacity is associated with pituitary pars intermedia oxidative stress and pituitary pars intermedia dysfunction (PPID) in horses. Methods: Blood samples from 20 horses with PPID and 20 healthy client-owned horses, archived paraffin-embedded adrenal gland and substantia nigra tissues from 20 horses, and pituitary gland tissue from 16 horses. Methods: Total glutathione, superoxide dismutase, and glutathione peroxidase activities were determined in RBCs. Accumulation of a systemic marker of oxidative stress (3-n...
Soffler C.Oxidative stress refers to the cellular injury and pathologic change that occurs when there is an imbalance favoring oxidants over antioxidants within a living organism. In human medicine, oxidative stress has been implicated in numerous disease processes, which has led to further research into the clinical benefits and efficacy of antioxidant therapy. The evaluation of oxidative stress in the horse has been limited primarily to ischemia-reperfusion injury of the gastrointestinal tract, recurrent airway obstruction, exercise, osteoarthritis, equine motor neuron disease, and pituitary pars inte...
Rendle DI, Litchfield E, Heller J, Hughes KJ.There is little published information on whether measurement of plasma ACTH concentration at a single timepoint is a repeatable indicator of pituitary pars intermedia dysfunction (PPID). Objective: To determine whether ultradian or circadian fluctuations in ACTH production influence plasma ACTH concentration in normal horses and horses with PPID. Methods: Prospective observational study. Methods: Plasma ACTH concentration in 8 non-PPID horses and 8 horses with PPID was measured at 08.00, 11.00, 14.00 and 17.00 h on 5 nonconsecutive days within a 3 week period. In addition, at 08.30 h on one da...
Beech J, McFarlane D, Lindborg S, Sojka JE, Boston RC.To compare endogenous ACTH and α-melanocyte-stimulating hormone (α-MSH) concentrations after administration of thyrotropin-releasing hormone (TRH) and to compare ACTH concentrations after TRH administration with those following domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction (PPID). Methods: Prospective case series. Methods: 69 clinically normal horses and 47 horses with or suspected to have PPID. Methods: ACTH concentrations were measured during 108 TRH stimulation tests in 88 horses, and α-MSH concentrations were measured during 56 TRH st...
McFarlane D, Donaldson MT, McDonnell SM, Cribb AE.To investigate effects of sample handling, storage, and collection time and season on plasma alpha-melanocyte-stimulating hormone (alpha-MSH) concentration in healthy equids. Methods: 11 healthy Standardbreds and 13 healthy semiferal ponies. Methods: Plasma alpha-MSH concentration was measured by use of radioimmunoassay. Effects of delayed processing were accessed by comparing alpha-MSH concentrations in plasma immediately separated with that of plasma obtained from blood samples that were stored at 4 degrees C for 8 or 48 hours before plasma was separated. Effects of suboptimal handling were ...
Restifo MM, Frank N, Hermida P, Sanchez-Londoño A.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...
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...
Rendle DI, Litchfield E, Gough S, Cowling A, Hughes KJ.Previous reports suggest that adrenocorticotrophic hormone (ACTH) degrades rapidly, limiting its use as a diagnostic test. Objective: This study quantified effects of processing delays on ACTH concentrations and investigated the addition of N-phenylmaleimide (maleimide), a protease inhibitor, as a means of reducing ACTH degradation. Methods: Experimental study. Methods: Venous blood was collected from 8 healthy horses and 8 horses with pituitary pars intermedia dysfunction (PPID) with a range of ACTH concentrations. Baseline ACTH concentrations were established immediately using a chemilumines...
Durham AE.Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin m...
Millington WR, Dybdal NO, Dawson R, Manzini C, Mueller GP.Equine Cushing's disease is caused by an adenomatous hyperplasia of the intermediate pituitary which secretes high levels of beta-endorphin, ACTH, and other peptide derivatives of POMC. In the present study we found that plasma and cerebrospinal fluid immunoreactive beta-endorphin (i beta-endorphin) levels were 60- and 120-fold higher than control values in horses with Cushing's disease. There were no significant differences in intermediate lobe i beta-endorphin concentrations, although anterior lobe i beta-endorphin was significantly reduced in Cushing's horses, presumably because high levels...
Muñoz MC, Doreste F, Ferrer O, González J, Montoya JA.A 16-year-old, male, Hanoverian horse had a three-month history of weight loss, hirsutism and polyuria/polydypsia. Examinations revealed neutrophilia, lymphopenia, hyper glycaemia and abnormalities in hepatic function. A tentative diagnosis of hyperadrenocorticism was made. The results of thyroid-releasing hormone and combined dexamethasone suppression and ACTH stimulation tests suggested the presence of a pituitary adenoma. The horse was treated with pergolide and beneficial clinical and biochemical responses were observed within one to six months.
Morgan RA, Keen JA, Homer N, Nixon M, McKinnon-Garvin AM, Moses-Williams JA, Davis SR, Hadoke PWF, Walker BR.Equine Cushing disease [pituitary pars intermedia dysfunction (PPID)] is a common condition of older horses, but its pathophysiology is complex and poorly understood. In contrast to pituitary-dependent hyperadrenocorticism in other species, PPID is characterized by elevated plasma ACTH but not elevated plasma cortisol. In this study, we address this paradox and the hypothesis that PPID is a syndrome of ACTH excess in which there is dysregulation of peripheral glucocorticoid metabolism and binding. In 14 horses with PPID compared with 15 healthy controls, we show that in plasma, cortisol levels...
McFarlane D, Hale GM, Johnson EM, Maxwell LK.To determine effects of pituitary pars intermedia dysfunction (Cushing's disease) and age on fecal egg count and time to egg reappearance after anthelmintic treatment in horses residing in similar environments. Methods: Cross-sectional study. Methods: 29 healthy horses (4 to 35 years old) and 13 horses with PPID (13 to 33 years old). Methods: Fecal egg counts were performed by use of a modified Wisconsin flotation method at 2-week intervals before and after ivermectin treatment. Results: Horses with PPID had higher fecal egg counts before and 8, 10, and 12 weeks after ivermectin treatment, com...
McFarlane D, Banse H, Knych HK, Maxwell LK.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 p...
Spelta CW.Equine pituitary pars intermedia dysfunction (PPID) is a neurodegenerative disease of the hypothalamus, resulting in the loss of dopaminergic inhibition of pars intermedia. An oxidative stress injury of unknown etiology has been suggested to initiate the neurodegeneration. While hypertrichosis (formerly known as hirsutism) is considered pathognomic for advanced disease, the antemortem diagnosis of subclinical and early disease has continued to prove difficult. Numerous tests have been used with varying sensitivities and specificities. The overnight dexamethasone suppression test, originally do...
Dunkel B, Wilford SA, Parkinson NJ, Ward C, Smith P, Grahame L, Brazil T, Schott HC.Severe hypertriglyceridaemia in horses and ponies with endocrine disorders has been reported anecdotally but has not been documented in the literature. Objective: To describe historical and clinicopathological findings as well as progression and outcome in horses and ponies with severe hypertriglyceridaemia (serum triglyceride concentration >5.65 mmol/l) secondary to an endocrine disorder that were otherwise apparently healthy. Methods: Cases from 6 participating institutions were identified and case details extracted from the medical records. Results: Case details of 3 horses and 4 ponies ...
Aleman M, Watson JL, Williams DC, LeCouteur RA, Nieto JE, Shelton GD.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 ...
McFarlane D, Miller LM, Craig LE, Dybdal NO, Habecker PL, Miller MA, Patterson JS, Cribb AE.To evaluate concordance among veterinary pathologists in the assessment of histologic findings in the pars intermedia of pituitary gland sections from aged horses with mild signs suggestive of pituitary pars intermedia dysfunction (PPID). Sample Population-10 pituitary glands from aged horses. Methods: 7 pathologists were provided with signalment, clinical signs, and a single H&E-stained pituitary gland section from 10 aged horses with mild signs suggestive of PPID. Pathologists described histologic findings for each section and stated whether findings were consistent with PPID. Agreement ...
Banse HE, Getachew F, Levy M, Smits J.Hair cortisol has been demonstrated to reflect hypothalamic-pituitary-adrenal axis activity (including Cushing's disease and stress) in several species. We hypothesized that hair cortisol concentrations are increased in horses with pituitary pars intermedia dysfunction (PPID) compared with healthy adult horses and that this difference is magnified in the fall, when circulating adrenocorticotropin (ACTH) is generally the highest. Cortisol from hair collected using clippers with a #40 blade from the neck was compared between PPID horses and control horses over several months in the fall (August-...
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...
Mejia-Pereira S, Perez-Ecija A, Buchanan BR, Toribio RE, Mendoza FJ.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. Objective: The objective of this study was to evaluate the previously described guidelines for PPID diagnosis in horses in donkeys with suspicion of PPID. Methods: 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 ...
Hofberger S, Gauff F, Licka T.In older horses, pituitary pars intermedia dysfunction (PPID) and suspensory ligament (SL) degeneration are common. The aim of the present study was to identify histopathological changes in the SL in horses with PPID. SLs of four horses with clinical signs of PPID (17-26 years of age) were compared with SLs from four old horses (18-31 years of age) and three young horses (4-9 years of age). In horses with PPID, there was reduced longitudinal arrangement of collagen fibres in SLs, along with inclusions of cartilage, extracellular matrix and haemorrhage, as well as significant proteoglycan accum...
McGowan CM, Neiger R.Trilostane, a competitive 3-beta hydroxysteroid dehydrogenase inhibitor, has been used successfully to control clinical signs and cortisol excess in canine pituitary dependent hyperadrenocorticism. Objective: Trilostane was evaluated for its efficacy in resolving clinical and clinicopathological abnormalities of equine Cushing's syndrome (ECS) and to assess its safety. Methods: Twenty horses (mean age 21 years) diagnosed with ECS were followed for 1 or 2 years. Affected horses received 0.4-1 mg/kg (mean 0.5 mg/kg) trilostane once daily. Results: Clinical signs assessed over 1 or 2 years, showe...
Spelta CW, Axon JE.The clinical manifestations of equine pituitary pars intermedia dysfunction (PPID) in temperate climates are well described. The classic presentation is that of an older animal with hirsutism, laminitis, poor muscle tone, pendulous abdomen and weight loss. This case series highlights the additional clinical signs of anhidrosis and heat stress with secondary exercise intolerance that were seen as primary presenting problems in equids with PPID in the hot, humid conditions of a tropical climate. The clinical signs resolved with medical treatment for PPID.
Siard-Altman MH, Harris PA, Moffett-Krotky AD, Ireland JL, Betancourt A, Barker VD, McMurry KE, Reedy SE, Adams AA.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 phenom...
Rendle DI, Duz M, Beech J, Parkin T, Durham AE.Paired measurement of ACTH concentration may be more reliable than a single measurement. Objective: To determine whether the mean of 2 measurements of ACTH concentration is more reliable in assessing pituitary pars intermedia dysfunction (PPID) than a single measurement. Methods: Paired ACTH measurements were performed on (1) 148 occasions from 124 horses being investigated for PPID, (2) 90 occasions from 76 horses with PPID that were receiving treatment with pergolide, and (3) 63 occasions from 50 horses in which there was no clinical suspicion of PPID. Histologic examination of the pars inte...
