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.
Mitsui I, Jackson LP, Couëtil LL, Lin TL, Ramos-Vara JA.A 13-year-old Quarterhorse mare had a 6-month history of diarrhea, progressive weight loss, and lethargy. At presentation the mare was hirsute, had hyperhidrosis, and abnormal fat distribution in addition to severe diarrhea. A presumptive clinical diagnosis of protein-losing enteropathy and pituitary pars intermedia dysfunction was made. T-cell lymphoma was diagnosed in a rectal biopsy specimen. The owner elected to euthanize the mare because of poor prognosis and the severity of the disease. At necropsy, the mare had hypertrichosis and the pituitary gland was diffusely enlarged. Histologicall...
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...
McFarlane D.Parkinson's disease (PD) is a leading cause of neurologic disability in the aged population. Remarkable progress has been made in the past decade to understand the cellular and molecular events that occur in PD. However attempts to unravel the early, initiating factors in the pathogenesis of dopaminergic neurodegeneration and PD have been limited by the lack of a suitable animal model. Models in which there has been genetic or environmental manipulation are not of use in determining the natural cause of a disease. While a large scale prospective human study would be ideal, the relatively low p...
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 ...
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...
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...
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 ...
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, Dybdal N, Donaldson MT, Miller L, Cribb AE.Equine pituitary pars intermedia dysfunction (PPID) is a spontaneously occurring progressive disease affecting aged horses and ponies. The pathogenesis of PPID is poorly understood, but the available evidence supports a loss of dopaminergic inhibition of the melanotropes of the pars intermedia. Horses with PPID have increased plasma concentrations of pars intermedia pro-opiomelanocortin-derived peptides that decrease in response to dopamine or dopamine agonist administration. Dopamine and dopamine metabolite concentrations are decreased in the pars intermedia of affected horses compared to age...
Schott HC.PPID in older equids has become a major health concern of horse owners. In response, equine practitioners have made greater efforts at understanding, diagnosing, and treating this disorder. Although PPID is recognized to be a different form of pituitary-dependent hyperadrenocorticism than is seen in canine or human patients, relatively little is known about the pathophysiology and natural progression of the disease. At present, the diagnosis is best supported by manifestation of characteristic clinical signs and endocrinologic test results, preferably a supportive DST result. Treatment must fo...
van der Kolk JH, Heinrichs M, van Amerongen JD, Stooker RC, in de Wal LJ, van den Ingh TS.To determine size and weight of the pituitary gland and associations between pituitary gland size and weight and sex and age in horses without clinical signs associated with pituitary pars intermedia adenoma (PPIA) and horses and ponies with PPIA. Methods: Pituitary glands from 100 horses without clinical signs of PPIA and 19 horses and 17 ponies with PPIA. Methods: Pituitary glands were weighed, measured, and examined histologically by use of H&E stain. Masson trichrome and periodic acid-Schiff staining were used, when appropriate. Histologic lesions in the pars intermedia, pars distalis,...
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 ...
McGowan CM, Frost R, Pfeiffer DU, Neiger R.Serum insulin concentration and its use as a prognostic indicator in horses with equine Cushing's syndrome (ECS) have been poorly documented. Objective: To examine daily insulin variations in horses with ECS and the effect of treatment using trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Further, we aimed to examine the relationship between baseline serum insulin concentration and survival in horses with ECS. Methods: Basal serum insulin concentrations were measured in 20 confirmed ECS cases by taking blood at regular 4 h intervals for 24 h (1200, 1600, 2000, 2400, ...
Keen JA, McLaren M, Chandler KJ, McGorum BC.The mechanisms underlying the increased risk of laminitis in horses with equine Cushing's disease (ECD) are poorly understood. Objective: That abnormalities in glucose homeostasis, similar to those which cause microvascular dysfunction in human diabetics, contribute to development of laminitis in horses with ECD. Methods: Thirty-one aged horses were divided into 3 groups based on clinical signs and dexamethasone suppression testing (DST). Group 1 (n = 12) had clinical ECD as evidenced by hirsutism. Group 2 (n = 10) had a positive DST but no hirsutism. Group 3 (n = 9) were controls without ECD,...
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...
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...
Brosnahan MM, Paradis MR.To describe the demographic and clinical characteristics of a population of geriatric horses. Methods: Retrospective study. Methods: 467 horses that were > or = 20 years of age. Methods: Medical records of 539 geriatric horses that were evaluated at a university large animal hospital between 1989 and 1999 were reviewed. Data collected included signalment, reason for evaluation, specific diagnoses, surgical procedures, inpatient or outpatient care, duration of hospitalization, and outcome. Results: 467 horses met the criteria for inclusion in the study. Horses that were > or = 20 years of age c...
Donaldson MT, LaMonte BH, Morresey P, Smith G, Beech J.Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 microg/kg p.o. q24h (range, 1.7-5.5 microg/kg). All horses treated with cyproheptadine were given 0.25 mg/kg p.o. q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml...
Perkins GA, Lamb S, Erb HN, Schanbacher B, Nydam DV, Divers TJ.Plasma ACTH levels have been variable in horses with a positive clinical response for therapy for equine Cushing's Disease (ECD). Therefore, our purpose was to determine the value of monitoring plasma adrenocorticotropin (ACTH) levels during treatment of equine Cushing's disease (ECD) with either cyproheptadine (n = 32) or pergolide (n = 10). First, we validated the chemiluminescent ACTH assay (specificity, precision, accuracy, intra-assay and interassay variations) and tested methods of handling the whole blood from the time of collection to when the ACTH was assayed. The sensitivity and spec...
Chandler KJ, Dixon RM.Urinary cortisol and creatinine concentrations, and the cortisol:creatinine ratio were compared between 12 healthy horses (group 1), 13 horses with Cushing's disease (group 2), and eight horses with dysautonomia syndrome (equine grass sickness) (group 3). The mean (sd) urinary cortisol concentrations were 112 (55.7), 250 (357) and 864 (526) nmol/litre in groups 1, 2 and 3, respectively; the mean (sd) urinary creatinine concentrations were 18.9 (7.3), 12.0 (6.7) and 45.2 (26.4) nmol/litre in groups 1, 2 and 3, respectively, and the mean (sd) ratios were 6.1 (2.6), 19.8 (23.8) and 21.3 (14.5) (x...
Reeves HJ, Lees R, McGowan CM.A high basal plasma or serum insulin concentration is commonly accepted as an indicator of Cushing's disease in horses. The results of the combined dexamethasone suppression test and thyrotropin-releasing hormone stimulation test were compared with the basal insulin concentrations and insulin response tests of eight hyperinsulinaemic and insulin-resistant ponies with clinical histories of chronic or recurrent laminitis that were suspected of having Cushing's disease. Seven of the eight ponies had normal responses to the combined test indicating that basal insulin concentrations are not a speci...
Harman J, Ward M.Equine Cushing's syndrome, a relatively common and complex condition, is difficult to treat with conventional medicine. Cushing's syndrome involves a hyperplasia or adenoma of the anterior pituitary gland. Biochemical alterations include increased endogenous cortisol, insulin resistance, elevated adrenocorticotrophic hormone, and decreased thyroid hormone levels. Symptoms include hirsutism with no loss of the winter coat in summer, refractory laminitis, weight problems (over- or underweight), polyuria/polydipsia (Pu/Pd), frequent infections, lowered immunity to intestinal parasites, decreased ...
van der Kolk JH, Wensing T.The urinary corticoid:creatinine (c:c) ratio was determined in ten pony mares suffering from hyperlipoproteinaemia. The mean (+/- sd) urinary c:c ratio of these ten ponies (47 +/- 31 x 10(-6)) was not significantly different from that of twelve pony mares with a pituitary pars intermedia adenoma (31 +/- 18 x 10(-6). The correlation between the urinary concentration of corticoids and plasma total lipids, and the correlation between the urinary c:c ratio and plasma total lipids in ponies with hyperlipoproteinaemia were not significant (P > 0.05; r = 0.53 and r = 0.008, respectively). Preliminary...
Fey K, Jonigkeit E, Moritz A.Equine and canine Cushing's syndrome, both of which are the result of elevated cortisol levels, show some different pathogenetical and clinical features and require different therapeutical approaches. In older horses the equine Cushing's syndrome (ECS) is not uncommon. Nearly all cases result from excessive hormone production in cells of the pars intermedia of the pituitary. Besides elevated levels of adrenocorticotrope hormone (ACTH), high peripheral levels of pro-opiomelanocortin, beta-endorphines and alpha-melanocyte-stimulating hormone can be measured. In middle-aged and geriatric dogs, Cu...
Okada T, Yuguchi K, Kiso Y, Morikawa Y, Nambo Y, Oikawa M, Sasaki F.The pars intermedia of the pituitary gland, and plasma ACTH and cortisol levels in the pony, which was first diagnosed in Japan as indicating equine Cushing's disease, were examined by immunohistochemistry and radioimmunoassay, respectively. The pars intermedia was greatly enlarged and most of its cells were immunoreactive for antisera to both adenocorticotropic hormone (ACTH) and beta-endorphin (beta-End). The plasma ACTH level was elevated when clinical symptoms appeared. The present results reveal that equine Cushing's disease in this pony was induced by the hypersecretion of ACTH and beta-...
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...
Hughes KJ, McGorum BC, Love S, Dixon PM.Six ponies and four horses with a mean (sd) age of 15.9 (6.0) years developed sudden-onset bilateral laryngeal paralysis (BLP) in association with hepatic dysfunction. Nine of them had been referred for the investigation of respiratory distress, and one pony had been referred for weight loss before BLP developed. Nine of the animals had clinicopathological evidence of liver disease, and nine had histological evidence of liver disease. All of the animals had one or more of the following: hepatic encephalopathy (in eight), hyperammonaemia (in six) and endoscopic evidence of BLP (in nine). Three ...
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.
Knowles EJ, Hyde C, Harris PA, Elliott J, Menzies-Gow NJ.A chemiluminescent immunoassay is commonly employed to measure adrenocorticotrophic hormone (ACTH) concentrations to assist pituitary pars intermedia dysfunction diagnosis. In a previous study, seasonally-dependent assay cross-reactivity to endogenous equine corticotropin-like intermediate lobe peptide (CLIP, ACTH 18-39) was suspected. The present study aimed to demonstrate binding of endogenous equine CLIP to the capture antibody of the ACTH chemiluminescent immunoassay. Liquid chromatography - mass spectrometry (LCMS) methods were optimised to identify selected ions from synthetic human ACTH...
Klinkhamer K, Menheere PP, van der Kolk JH.Glucocorticoids are suggested to precipitate laminitis and induce insulin resistance in horses. Objective: To assess insulin sensitivity and the basal amount of glucose metabolized in equine pituitary pars intermedia dysfunction (PPID). Methods: The euglycaemic hyperinsulinaemic clamp (EHC) technique was performed in seven horses with a diagnosis of PPID based on the presence of hypertrichosis and positive dexamethasone suppression-test results comprising one gelding and six mares with a mean age of 21.1 ± 5.8 (SD; range 15-34) years. Results were compared with those from five negative (h...
Peel AJ, Bouts T, Flach E, Rivers S, Routh A.Pituitary pars intermedia dysfunction (PPID), also known as Equine Cushing's disease, is most often diagnosed in older horses and ponies. To the authors' knowledge, there have been no reports of its diagnosis in captive nondomestic equids. A 13-yr old onager (Equus hemionus onager) at the Zoological Society of London (ZSL) Whipsnade Zoo showed clinical signs suggestive of PPID, including hirsutism, fat redistribution, weight loss, laminitis, and chronic infections. A dexamethasone suppression test was performed to confirm PPID. Subsequently, adenomatous hyperplasia and microadenoma of the pars...
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.
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 ...
Shank BR, Ofner CM.Pergolide mesylate (proprietary name Permax) is used to treat equine Cushing's syndrome. Since pergolide mesylate has been removed from the market, the tablets are no longer available. Therefore, pergolide mesylate preparations have to be compounded for veterinary use. Compounded oral liquid formulations have been given arbitrary beyond-use dates of 14 days (aqueous) to 90 days (oil based). The goal of this study was to determine the stability of a 0.2 mg/mL pergolide oral liquid prepared according to a previousy published formulation and stored at room temperature. The sample preparation and ...
Randleff-Rasmussen PK, Mosca M, Knoerr F, Pin D, Desjardins I.Mycetoma is a chronic, proliferative lesion of cutaneous/subcutaneous tissue characterized by draining tracts and granules in the discharge caused by actinomycetes (actinomycetoma) or filamentous fungi (eumycotic mycetoma). Objective: This case report describes the unusual finding of a cutaneous mycetoma of the lateral wing of the right nostril in a gelding. Methods: A 16-year-old Fjord gelding with suspected pituitary pars intermedia dysfunction (PPID) was presented for evaluation of a nonpainful, firm and raised mass involving the lateral wing of the right nostril and the lip. Results: Cytol...
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...
Fisher D, Schliewert EC, Hooijberg EH.An endogenous adrenocorticotropic hormone (ACTH) concentration above the reference interval (RI) is commonly used as means for diagnosing equine pituitary pars intermedia dysfunction (PPID). Basal ACTH concentrations are highly dependent on photoperiod and RIs should be month- and location-specific. To date, no ACTH RIs have been specifically established for South Africa. This study aimed to determine geographically and seasonally relevant RIs for equine ACTH in the Gauteng province of South Africa. A longitudinal prospective study was conducted over twelve months to determine ACTH RIs for a r...
Shepard MK, Lee WL, Eggleston RB.A 21-year-old Thoroughbred gelding with a history of equine pituitary pars intermedia dysfunction (PPID) presented with priapism of 2 days' duration. The horse received a caudal morphine epidural and then underwent corpus cavernosum lavage and phallectomy under general anesthesia. The patient's recovery featured multiple unsuccessful attempts to stand and his respiratory distress persisted for several hours until he acutely developed severe colic and was euthanized. Necropsy findings revealed a pituitary adenoma of the pars intermedia, bilateral adrenal cortical hyperplasia, and diaphragmatic ...
Sakes A, Arkenbout EA, JelÃnek F, van der Kolk JH, Breedveld P.A new paradigm of surgical treatment of equine Cushing's disease has been developed using the vascular system combined with a flexible morcellation instrument to reach the pituitary gland. Objective: The goal was twofold: (1) to design, prototype, and test an instrument that can reach the pituitary gland using the vascular system unique to equids and (2) to test the feasibility of the endovascular approach. Methods: The morcellator consists of a radial rotating cutting blade for tissue resection, a flexible shaft incorporating a cable drive for flexible actuation, and central morcellated tissu...
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.
Bamford NJ, Stewart AJ, El-Hage CM, Bertin FR, Bailey SR.Plasma adrenocorticotropic hormone (ACTH) concentration is commonly measured to diagnose pituitary pars intermedia dysfunction (PPID). Several intrinsic and extrinsic factors affect ACTH concentrations, including breed. The objective of this study was to prospectively compare plasma ACTH concentrations among different breeds of mature horses and ponies. Three breed groups comprised Thoroughbred horses (n = 127), Shetland ponies (n = 131) and ponies of non-Shetland breeds (n = 141). Enrolled animals did not show any signs of illness, lameness or clinical signs consistent with PPID. Blood ...
Frank N, Tadros EM.Abnormalities of insulin metabolism include hyperinsulinaemia and insulin resistance, and these problems are collectively referred to as insulin dysregulation in this review. Insulin dysregulation is a key component of equine metabolic syndrome: a collection of endocrine and metabolic abnormalities associated with the development of laminitis in horses, ponies and donkeys. Insulin dysregulation can also accompany prematurity and systemic illness in foals. Causes of insulin resistance are discussed, including pathological conditions of obesity, systemic inflammation and pituitary pars intermedi...
Vorster DM, Wang W, Kemp KL, Bamford NJ, Bertin FR.The thyrotropin-releasing hormone (TRH) stimulation test is used to diagnose pituitary pars intermedia dysfunction (PPID) using 10- or 30-min protocols. Imprecise sampling time for the 10-min protocol can lead to misdiagnoses. Objective: To determine the effect of imprecise sampling time for the 30-min protocol of the TRH stimulation test. Methods: In vivo experiment. Methods: Plasma immunoreactive adrenocorticotropin (ACTH) concentrations were measured 9, 10, 11, 29, 30 and 31 min after intravenous administration of 1 mg of TRH in 15 control and 12 PPID horses. Differences in ACTH concent...
Rendle DI, Hughes KJ, Doran GS, Edwards SH.To determine the pharmacokinetics of pergolide after IV administration to horses. Methods: 8 healthy adult horses. Methods: Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. Results: After IV administration of pergolide, mean ± SD clearance, elimination half-life, a...
Beech J, Boston R, Lindborg S, Russell GE.To compare the effect of thyrotropin-releasing hormone (TRH) administration on endogenous ACTH concentrations in healthy horses and those with pituitary pars inter-media hyperplasia and compare the test with the dexamethasone suppression test (DST). Methods: Prospective case series. Methods: 15 horses with clinical signs of pituitary pars intermedia dysfunction (PPID), 4 horses with equivocal signs of PPID, and 29 horses without signs of PPID. Methods: ACTH concentrations prior to and after administration of TRH were measured 61 times in 48 horses. Results of the DST (cortisol response) were c...
Stewart AJ, Ireland JL, Durham AE, McGowan CM.Equine pituitary pars intermedia dysfunction (PPID) is common in aged horses. The majority of horses respond well to treatment, but treatment is lifelong, meaning accurate diagnosis of PPID is important. Similar to any condition, there is no perfect laboratory test to diagnose PPID and accuracy is affected by the characteristics of the population in which the test is being evaluated. This review details the importance of consideration of clinical factors and diagnostic test accuracy. Basal adrenocorticotrophic hormone (ACTH) concentration is used most frequently in practice and has very good d...
de Laat MA, Sillence MN.Blood glucose concentration is often measured during an oral glucose test (OGT), but is not thought to aid in diagnosing insulin dysregulation (ID) or pituitary pars intermedia dysfunction (PPID). The aim of this retrospective study was to investigate whether the change in blood glucose concentration during an OGT aligned with indicators of equine metabolic syndrome or PPID, including serum insulin and plasma ACTH concentrations, clinical observations, age, sex, breed type and the test dose. The cohort included 149 horses, miniature horses, and ponies that had undergone an in-feed OGT and clin...
Adams AA, Siard-Altman MH, Reedy SE, Barker D, Elzinga S, Sanz MG, Urschel K, Ireland JL.Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation test has been recommended for diagnosis of early or mild cases. However, it is currently not recommended for year-round use due to marked seasonal variability. The aims of this cohort study were to evaluate effects of month and season on adrenocorticotropic hormone (ACTH) responses to TRH stimulation and to derive monthly cut-offs for PPID d...
Drozdzewska K, Winter J, Barton AK, Merle R, Gehlen H.The basal (bACTH) and post-thyrotropin-releasing hormone stimulation concentration of adrenocorticotropin (pACTH) are recommended for diagnosis of pituitary pars intermedia dysfunction (PPID). Many factors influence bACTH (e.g., disease, age, month) and some affect the results only in autumn (e.g., breed, colour, sex). There are discrepancies about the impact of feeding on b/pACTH. Objective: To determine whether feeding, month, age, breed, colour, sex and body condition score affect b/pACTH. Methods: Prospective crossover. Methods: Sixty-one animals were divided into groups: healthy, PPID, tr...
Colbath AC, Fortin JS, Burglass CM, Panek C, Vergara-Hernandez FB, Johnson TN, Robison CA, Logan AA, Nelson NA, Nielsen BD, Schott HC.Pathological fractures have been reported in equids with pituitary pars intermedia dysfunction (PPID) but their prevalence and pathogenesis is unknown. Objective: To compare: (1) bone mineral density (BMD) in weight bearing and nonweight bearing bones in PPID+ equids and aged and young PPID- controls; and (2) biomechanical properties of the fourth lumbar vertebral body in PPID+ equids and aged PPID- equids. Methods: Case-control study: five PPID+ equids and six aged and four young PPID- control horses. Methods: PPID status was based on clinical signs and necropsy examination of the pituitary g...
Clark BL, Norton EM, Bamford NJ, Randhawa IAS, Kemp KL, McCue ME, Bertin FR, Stewart AJ.Insulin dysregulation (ID) is central to equine metabolic syndrome. There are limited epidemiological studies investigating dynamic testing of ID in ponies. Objective: To evaluate prevalence and risk factors for ID through dynamic testing of hyperinsulinaemia (DHI) and insulin resistance (IR). Methods: Cross-sectional. Methods: Sex, age, breed, height, cresty neck score (CNS), body condition score (BCS), laminitis, HMGA2:c.83G>A genotype and pituitary pars intermedia dysfunction (PPID) status were documented. Dynamic hyperinsulinaemia was diagnosed with an oral sugar test (OST) and IR with an ...
Ireland JL, Lester A, Banse HE.Measurement of basal adrenocorticotropic hormone (ACTH) concentration is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID). Although several pre-analytical and analytical factors have been reported to affect basal ACTH concentrations in equids, the extent to which these have been evaluated in the context of PPID diagnosis is unclear. The objectives of this scoping review were to identify and systematically chart current evidence about pre-analytical and analytical factors affecting basal ACTH concentrations in adult domestic equids. Systematic searches of ...
Waitt Wolker LH, Black A, Lee JK.Clinical and histologic examination of a 12-y-old client-owned Quarter Horse gelding with pituitary pars intermedia dysfunction revealed dermatitis, cellulitis, and osteomyelitis caused by , confirmed by a PCR assay. This novel presentation of a fungal disease in a horse was characterized by aggressive local invasion and failure to respond to all medical therapy attempted over a 1-y period. Treatments included systemic and topical antifungals, anti-inflammatories, and use of cellular matrices. Surgical excision was not attempted but should be strongly considered early in the disease process in...
Sundra T, Kelty E, Rossi G, Rendle D.Dopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. However, some horses are refractory to daily oral pergolide, the recommended registered treatment. Extended-release cabergoline (ERC) injection may offer an alternative. The objective of this retrospective case series was to describe clinical and endocrinological responses to ERC. Unassigned: Medical records of horses treated with weekly intramuscular injections of ERC (5 mg/mL, BOVA Aus) at either 0.01 mg/kg (high dose, HD) ( = 10) or 0.005 mg/kg (low dose, LD) ( = 30) w...
