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.
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...
Barrell EA.Polyuria and polydipsia are rare, but significant, manifestations of several different diseases of horses. Causes can be endocrine, iatrogenic, psychogenic, infectious, or toxic in nature and can also be due to primary renal disease or diseases of other organs, such as the liver. Although numerous causes of polyuria and polydipsia in horses exist, the most common conditions include chronic kidney disease, pituitary pars intermedia dysfunction, and psychogenic polydipsia with secondary polyuria. Additional testing is dictated by history, other clinical signs, and the results of blood work and/o...
Hobbs KJ, Porter E, Wait C, Dark M, MacKay RJ.Magnetic resonance imaging is increasingly available for evaluation of horses with suspected pituitary adenomas; however, published studies describing the MRI features of normal equine pituitary glands are currently lacking. This retrospective, descriptive, anatomic study describes the MRI appearance and size of presumed normal equine pituitary glands and assesses potential correlations between pituitary size, brain size, and patient weight. These findings serve as a reference for MRI evaluation of the equine pituitary gland. Inclusion criteria consisted of adult horses (2-15 years old), over ...
Nichols JL, Robinson JS, Hiney KM, Terry R, Ramsey JW.This study investigated equine nutrition knowledge and educational needs of licensed veterinarians in the United States who were exclusively or predominately equine practitioners. It found veterinarians regard their peers as an important resource of nutritional knowledge, ranking ahead of all other sources except a PhD equine nutritionist. Interestingly, only 21% of veterinarians felt good about their knowledge level in equine nutrition after graduating from veterinary school. Although veterinarians in this study reported equine nutrition to be an area of weakness, 75% had not pursued continui...
Hinrichsen SL, Yuen KY, Dryburgh EL, Bertin FR, Stewart AJ.Pituitary pars intermedia dysfunction (PPID) is diagnosed by increased basal or post thyrotropin-releasing hormone (TRH) stimulation ACTH concentrations. ACTH is known to be unstable; however, the effect of different temperatures and TRH stimulation on equine ACTH stability is poorly described. In total, 15 horses, including 8 PPID positive (ACTH > 35 pg/mL at baseline or >65 pg/mL 30 min after TRH stimulation), were divided into 2 groups: 9, including 5 PPID positive, with basal ACTH concentrations and 6, including 3 PPID positive, with post TRH stimulation ACTH concentrations. Whole bl...
Nitzsche AM, Fey K, Büttner K, Gröf M, Staszyk C.Pituitary pars intermedia dysfunction (PPID) is a common neurodegenerative disease mainly in horses older than 15 years. The domestic equine population is following the same demographic change as that seen in humans; it is aging and veterinarians are asked to attend to geriatric horses more frequently. Common problems seen regularly in older equines are dental disorders and especially periodontal disease. As a systemic and endocrine disease, associated with delayed wound healing and impaired immune function, PPID should be considered before major dental treatment in aged equines is started. Po...
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...
Johnson PJ, Wiedmeyer CE, Messer NT, Ganjam VK.There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attribut...
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...
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...
Ireland JL, McGowan CM.Pituitary pars intermedia dysfunction (PPID) is caused by an age-related degenerative disease of dopaminergic neurones. Despite its importance in equine practice, available information regarding its epidemiology is limited. This systematic review aimed to assess published literature to evaluate available evidence regarding the clinical presentation, prevalence and risk factors for PPID in horses and ponies. Electronic database searches were undertaken using a range of terms, and English language publications published prior to August 2016 were included. Both authors independently reviewed scre...
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 ...
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...
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...
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...
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 ...
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 (...
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...
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...
