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.
Eiler H, Oliver JW, Andrews FM, Fecteau KA, Green EM, McCracken M.To evaluate results of a combined dexamethasone suppression/thyrotropin-releasing hormone (TRH) stimulation test in horses suspected clinically to have a pars intermedia pituitary adenoma (PIPA). Methods: Case-control study. Methods: 7 healthy adult horses and 5 horses suspected to have a PIPA. Methods: A baseline blood sample was collected, and dexamethasone (40 micrograms/kg [18 micrograms/lb] of body weight, IV) was administered; a second blood sample was collected 3 hours later, and TRH (1.1 mg, IV) was administered; serial blood samples were collected 15, 30, 45, 60, and 90 minutes and 21...
Carrasco L, Mendez A, Jensen HE.An atypical case of chronic equine bronchopulmonary aspergillosis with an unusual hyphal morphology was diagnosed in a horse with Cushing's syndrome. Because of the hyphal localization in chronic ectatic bronchi and bronchioles, and juxtabronchiolar processes, the observed type of aspergillosis is similar to 'saprophytic bronchopulmonary aspergillosis' or 'semi-invasive pulmonary aspergillosis' in humans. The aetiological diagnosis of aspergillosis was accomplished by the application of a panel of monospecific polyclonal and monoclonal antibodies in immunohistochemical techniques.
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.
Couëtil L, Paradis MR, Knoll J.Pituitary adenomas are commonly reported in older horses. The typical clinical signs associated with this condition, also known as equine Cushing's disease (ECD), are related to increased adrenocorticotropin (ACTH) production resulting in hyperadrenocorticism. The primary purpose of this study was to determine whether plasma ACTH concentrations differed between cushingoid and healthy horses. The second objective was to determine the effects of blood sample handling techniques on ACTH concentrations. A commercial human ACTH radioimmunoassay (RIA) was used to quantify equine plasma ACTH. Intra-a...
van der Kolk JH, Wensing T, Kalsbeek HC, Breukink HJ.Lipid metabolism was studied in 21 horses with hyperadrenocorticism. To be included in the study, horses had to have histologic evidence of a pars intermedia adenoma found at necropsy (n = 9), a baseline ACTH concentration greater than 400 pg/ml (n = 6), or a plasma cortisol concentration 2 hours after i.v. administration of 25 IU of ACTH greater than 413 nmol/L (n = 16). Mean +/- SD baseline plasma cortisol concentration was 338 +/- 261 nmol/L (n = 20), mean +/- SD plasma insulin concentration was 97 +/- 54 microU/ml (n = 15), mean +/- SD plasma beta-hydroxybutyrate concentration was 1.8 +/- ...
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 (...
van der Kolk JH, Kalsbeek HC, Wensing T, Breukink HJ.The urinary corticoid:creatinine (c:c) ratio was determined in eight horses with hyperadrenocorticism (HAC). The mean (+/- SD) urinary c:c ratio of the eight horses with HAC (29 +/- 14 x 10(-6)) was significantly (P < 0.05) greater than the ratio in seven control horses (11 +/- 4.3 x 10(-6)). The urinary concentration of corticoids in control horses (201 +/- 60.4 nmol litre-1) was significantly (P 0.05) between both groups. As both false negative and false positive cases were found, it is concluded that a measurement of the urinary c:c ratio in the horse should not be used as the sole test...
van der Kolk JH, van Hoorn CJ, van Garderen E, van den Belt AJ.An eighteen-year-old pony gelding was referred to the Faculty of Veterinary Medicine because of colic, due to cecal tympany. His haircoat was dull with long wavy hair. After medical treatment of the colic it was sent home three days later. Just before it had been dismissed the morning plasma glucose concentration measured 10.2 mmol.l-1. The basal plasma cortisol concentration was high (180 nmol.l1) and basal plasma ACTH concentration was highly elevated (> 960 pg.ml1). An ACTH-stimulation test was performed by intravenous administering of 0.25 mg synthetic ACTH 1 24 at 9.00 hours showing ad...
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...
van der Kolk JH, Klein WR, van der Putten SW, Mol JA.A thirteen-year-old Dutch warmblooded mare was referred to the Faculty of Veterinary Medicine because of a sinusitis. She was thin with a potbellied appearance. Her coat was dull with long wavy hair. Unilateral (left) purulent nasal discharge was evident. A cbc revealed leucopenia (3.9 G.L.-1) and plasma biochemical analysis revealed a plasma glucose concentration of 10.1 mmol.L-1. Thermostable alkaline phosphatase (at 65 degrees C during 2 minutes) could not be demonstrated. Basal plasma cortisol concentration was lowered (114 nmol.L-1) and basal plasma ACTH concentration was highly elevated ...
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...
Auer DE, Wilson RG, Groenendyk S, Filippich LJ.A case of pituitary dependent hyperadrenocorticism in a horse is reported. Clinical signs included hirsutism, polydipsia and general debility. The horse was persistently hyperglycaemic and glucose values were unchanged following subcutaneous administration of insulin. Resting cortisol values were normal, but dexamethasone suppression of cortisol concentration was shorter than normal. Plasma glucose, cortisol, insulin and glucagon concentrations were measured as part of an intravenous glucose tolerance test. The patient responses were different from those in a control pony.
Orth DN, Nicholson WE.Equine Cushing's disease is caused by hypersecretion of ACTH by hyperplasia or adenomas of pars intermedia (PI) cells, in contrast to human Cushing's disease, which is caused by hyperplasia or adenomas of pars distalis (PD) ACTH-secreting cells. We assayed both bioactive and immunoreactive (IR) ACTH in two normal equine pituitary glands and in the PD, PI, and pars nervosa of four such glands, as well as in the PI adenomas of five horses with Cushing's disease. In normal horse pituitaries, as in those of other species, most of the bioactive and IR-ACTH was found in PD, much less in PI, and only...
Nielsen MK, Finnerty CA, Ripley NE, Page AE, McClendon ME, Adams AA.Anthelmintic performance against equine cyathostomins can be evaluated by two different non-terminal measures; the Fecal Egg Count Reduction Test (FECRT) and the Egg Reappearance Period (ERP). Most available FECRT and ERP data have been determined in populations of young horses, and very little information is available from mature and senior horses. Furthermore, it is unknown how commonly occurring equine endocrine disorders such as Insulin dysregulation (ID) and Pituitary pars intermedia dysfunction (PPID) may interfere with these measurements, but it has been suggested that horses with these...
Horner A, Bamford NJ, Stear MJ, Piedrafita D, Jabbar A, Hughes KJ, El-Hage CM, Preston S.Pituitary pars intermedia dysfunction (PPID) is the most common endocrine disorder of older horses. Immune dysfunction in horses with PPID could increase susceptibility to infectious diseases, including strongyle infections; however, few data are available. The aim of this study was to determine if horses with PPID had increased strongyle faecal egg counts (FEC) compared with control horses, over a fourteen-week period in Victoria, Australia. Clinical signs and plasma adrenocorticotropic hormone (ACTH) concentrations were used to categorise horses into PPID (n=14) or control (n=31) groups. Fae...
Hallowell KL, Dembek K, Horne CR, Knych HK, Messenger KM, Schnabel LV.Steroid-associated laminitis remains a major concern with use of corticosteroids in horses. Individual case factors such as joint pathology, pre-existing endocrinopathies, or corticosteroid type, dose, and timing influencing steroid-induced laminitis risk have not been investigated. This study aimed to determine if systemic absorption of triamcinolone acetonide (TA) varies between intrasynovial (antebrachiocarpal) and extrasynovial (sacroiliac) injection sites, and to determine the effects of TA absorption on glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH). Twenty adult hors...
Herbst AC, Coleman MC, Macon EL, Harris PA, Adams AA.Information on health care and health status of U.S. senior horses (≥15 years of age) is currently sparse. Objective: (A) Provide an overview of owner-reported (1) medical conditions, (2) management/treatment practices for equine metabolic syndrome and pituitary pars intermedia dysfunction (PPID), (3) frequencies of routine health care practices and (4) supplement and pharmaceutical use in U.S. senior horses (≥15 years of age). (B) Evaluate potential risk factors for certain medical conditions and for low routine health care. Methods: Online survey. Methods: Descriptive and inferential...
Neufang L, Ramos J, Eda S, Flatland B, Giori L.Pituitary pars intermedia dysfunction (PPID) is a neurodegenerative disease of senior horses. Loss of dopaminergic inhibition of the melanotropes of the pars intermedia leads to increased concentrations of pro-opiomelanocortin (POMC)-derived peptides. Diagnosis is challenging due to pre-analytical variables, such as sample storage, handling, and time to analysis. Our objective was to develop an ELISA for ACTH measurement, which could ultimately form the basis for a stall-side equine ACTH test. We selected 2 ACTH-specific monoclonal antibodies, CBL57 and EPR20361-248, based on the recognition o...
Cash CM, de Laat MA.The melanocortin 2 receptor (MC2R) has relevance to equine pituitary pars intermedia dysfunction (PPID), as it is the primary binding site for ACTH, which circulates at elevated concentrations in animals affected by PPID. Despite this, little is known about MC2R in equine species. The overall aim of this investigation was to determine MC2R mRNA expression in tissues relevant to PPID in healthy horses and to examine the MC2R gene sequence in a cohort of horses and ponies with and without PPID. The study found that the MC2R gene was expressed in both adrenal and pituitary gland tissues as report...
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...
Galinelli NC, Bamford NJ, Erdody ML, Warnken T, de Laat MA, Sillence MN, Harris PA, Bailey SR.The role of dopamine in the regulation of insulin secretion in horses is poorly understood and requires further investigation. Pituitary pars intermedia dysfunction (PPID) is associated with decreased activity of dopaminergic neurons which normally suppress peptide hormone secretion from the pituitary pars intermedia. A high proportion of horses with PPID also have insulin dysregulation (ID), characterised by post-prandial hyperinsulinaemia and/or tissue insulin resistance, which are risk factors for the development of laminitis. The aim of this study was to investigate the effects of alpha-me...
Jargielo MM, Kritchevsky JE, Bertin FR.Pergolide, labeled for the treatment of pituitary pars intermedia dysfunction, is 90% protein bound and might cause a decrease in blood thyroid hormone concentrations by displacing them from binding proteins. This study investigated the effect of pergolide on the equine thyroid function. Methods: This was an analytic, observational, cohort study. Six horses (17 to 24 years old and 530 to 599 kg) received 1 mg of pergolide mesylate orally once a day from days 1 to 6. Total T4 (tT4) was measured daily from day 0 to 11 (before, during, and after pergolide treatment). Thyrotropin-releasing hormone...
Johnston TJ, Stewart AJ, Dryburgh EL, Bertin FR.Pituitary pars intermedia dysfunction (PPID) is diagnosed by measuring the ACTH concentrations. Due to the reported instability of ACTH, it is recommended to transfer centrifuged plasma into cryovials; however, in practice, cryovials are infrequently used, and serum (red-top) tubes are used instead. This study investigated whether this procedure affects ACTH concentrations and the diagnosis of PPID. Unassigned: This was a cohort study. Blood was collected into EDTA tubes from 9 horses with PPID and 7 controls. After centrifugation, plasma was either aliquoted into a cryovial or into a serum tu...
Maier I, Kienzle E.The goal of this meta-analysis was to (i) identify any potential differences in the apparent and true digestibility, renal excretion, and retention between ponies and horses and (ii) examine the impact of work on these parameters. Additionally, the study aimed to (iii) evaluate the effects of water deficiency. This meta-analysis used data from 33 studies and plotted them in diagrams similar to the Lucas test against mineral intake. Three studies involved ponies that were later diagnosed with pituitary pars intermedia dysfunction (PPID). These were compared with other data to identify quantitat...
Wang W, Gibson J, Horsman S, Mikkelsen D, Bertin FR.Altered gut microbiota has been associated with dopaminergic degenerative diseases in people, but studies on horses with pituitary pars intermedia dysfunction (PPID) are lacking. Objective: Investigate the effect of PPID on fecal microbiota in horses. Methods: Nine horses with PPID and 13 age-matched control horses. Methods: Prospective control study. Fecal samples were collected bimonthly. Microbial analysis used 16S rRNA sequencing to determine the relative abundance at genus and phylum levels, assess alpha and beta diversity and identify core microbiota. Results: Horses with PPID had decrea...
Galinelli NC, Bamford NJ, Erdody ML, Mackenzie SA, Warnken T, Harris PA, Sillence MN, Bailey SR.Due to the high frequency of laminitis reported for both conditions, the relationship between pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID), and the potential role of dopamine in modifying insulin secretion, requires further investigation. Objective: To evaluate the effect of pergolide mesylate on insulin sensitivity and postprandial insulin and glucose responses in horses and ponies with ID, both with or without concurrent PPID. Methods: Randomised crossover study. Methods: Sixteen horses and ponies, comprising eight matched pairs (PPID+ID or ID-only), were given...
Fouché N, Doras C, Schüpbach-Regula G, Scherer A, Freudenschuss B, Gerber V.There remains a scarcity of data concerning the relationship between the clinical signs associated with PPID and plasma ACTH concentrations. Objective: Report the frequency of clinical signs in the study cohort and identify individual clinical signs or combinations of clinical signs associated with high ACTH concentrations. Methods: Two hundred eighty equids were examined by private veterinarians. Methods: A cross-sectional study of animals with clinical suspicion of PPID was conducted between August and November. Private practitioners completed an online questionnaire reporting detailed infor...
Stapley ED, Bertin FR.Pituitary pars intermedia dysfunction is diagnosed using immunoreactive ACTH concentrations. Glass reportedly binds ACTH, but the clinical relevance of using glass blood tubes for measuring equine ACTH concentrations is controversial. This study investigates whether the collection of whole blood into glass EDTA tubes and storage for up to 6 hours changes ACTH concentrations compared to plastic EDTA tubes. Unassigned: This was a cohort study. Whole blood was collected into both glass and plastic EDTA tubes from 9 horses > 12 years of age, including 4 with pituitary pars intermedia dysfunction a...
Davis EL, Wood AD, Potier JFN.Prevalence of endocrine disease in sport horses has been sparsely reported. They often compete well into their teenage years; thus, diagnosis and control of endocrine disease could be important to maintain performance and optimise health and welfare. The aim was to compare the prevalence of pituitary pars intermedia dysfunction (PPID), insulin dysregulation (ID) and metabolic obesity between sport and non-sport type breeds and assess disease progression. Blood samples submitted for plasma adrenocorticotropic hormone (ACTH), serum insulin or adiponectin were included in this study. Horses were ...
Bouquet A, Nicol C, Knowles EJ, Schofield I, Menzies-Gow NJ.Clinical signs of pituitary pars intermedia dysfunction (PPID) are frequently mistaken for 'normal' ageing and may not be optimally assessed. Objective quality of life (QoL) assessment could improve clinical decision-making. Objective: To develop an owner-reported health-related quality-of-life (HRQoL) assessment tool for equines with PPID. To assess factors associated with HRQoL scores. Methods: Quantitative, cross-sectional study. Methods: HRQoL tool development followed a standard psychometric process of item (any aspect of PPID and its management that could impact QoL) identification (foll...
Schott HC, Strachota JR, Marteniuk JV, Refsal KR.Limited data document long-term responses of equids with pituitary pars intermedia dysfunction (PPID) to pergolide treatment. Objective: Report clinical response, medical problems, outcome, and owner satisfaction with pergolide treatment of PPID-affected equids over 14 years. Methods: Thirty client-owned equids with PPID. Methods: After completion of an open field clinical efficacy study for Prascend® (pergolide tablets), 28 horses and two ponies were enrolled in an extended treatment study (13 receiving 2 μg/kg PO q24h and 17 receiving 4 μg/kg PO q24h). Clients were interviewed eve...
Osorio-Cardona JJ, Usuga-Moreno VM, Martínez-Aranzales JR.The dexamethasone suppression test (DST) has been used in humans for the diagnosis of psychiatric problems such as depression, anxiety and Cushing's syndrome, and in horses for the ante mortem diagnosis of dysfunction of the intermediate part of the pituitary. Objective: This study aimed to examine the functionality of the hypothalamic-pituitary-adrenal axis through the DST and the cortisol index (CI), to evaluate the rhythmicity of the circadian cycle of cortisol in healthy horses with crib-biting or windsucking. Methods: A total of 20 Colombian Creole horses of both sexes, under similar mana...
Tretow M, Hain AM, Bienert-Zeit A.The dental syndrome EOTRH is a painful, progressive dental disease with an unknown aetiology. The often painful nature of EOTRH emphasises the need for a better knowledge of the underlying pathogenic mechanism and risk factors. A comparative analysis of haematological, biochemical and endocrine values in EOTRH-affected and non-affected horses has not been described. Objective: To compare haematological, biochemical, and endocrine parameters in EOTRH-affected and non-affected horses to detect risk factors for horses developing EOTRH. Methods: Cross sectional. Methods: Blood samples of 154 Icela...
Murase H, Wachi S, Matsuyama R, Makita K, Sato F.Pituitary pars intermedia dysfunction (PPID) is an age-related disease considered to have a negative impact on fertility. To understand the true impact of PPID on fertility, the influence of age must be considered. Objective: This study aimed to assess the impact of PPID on fertility while accounting for the effect of aging. Methods: A total of 332 Thoroughbred mares aged 10-20 years and managed across 137 private farms in Hidaka, Hokkaido, Japan were classified as PPID, equivocal, or non-PPID based on plasma adrenocorticotropic hormone concentration in 2019 and 2020. The prevalence of PPID an...
