Topic:Pituitary Pars Intermedia Dysfunction
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.
Bilateral laryngeal paralysis associated with hepatic dysfunction and hepatic encephalopathy in six ponies and four horses. 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 ...
Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing’s disease under natural photoperiod. 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...
Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction. 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...
Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction. 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 ...
Factors affecting clinical assessment of insulin sensitivity in horses. 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...
Equine’s Cushing’s Disease: A Clinical Update. The Department of Pharmacology at the North Carolina State University College of Veterinary Medicine is currently conducting stability studies of oral suspensions of pergolide for the treatment of Cushing's disease. While those results are not available at this time, this paper summarizes the results of a literature search on possible clinical treatments for equine Cushing's and is intended to provide insight into the pathophysiology of the disease. Pharmacological options for treatment of equine Cushing's are discussed.
Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia. 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...
Evidence-based literature pertaining to thyroid dysfunction and Cushing’s syndrome in the horse. The evidence-based literature pertaining to thyroid dysfunction and Cushing's syndrome is discussed in this article. Summaries of and recommendations for the treatment of these conditions are made. There is a need for reliable diagnostic tests for these conditions in horses.
Hypertrichosis in a horse with alimentary T-cell lymphoma and pituitary involvement. 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...
Oxidative stress. 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...
Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease. 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...
Myopathy in horses with pituitary pars intermedia dysfunction (Cushing’s disease). 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 ...
Evaluation of the combined dexamethasone suppression/ thyrotropin-releasing hormone stimulation test for detection of pars intermedia pituitary adenomas in horses. 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...
Systemic and pituitary pars intermedia antioxidant capacity associated with pars intermedia oxidative stress and dysfunction in horses. 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...
Agreement in histologic assessments of the pituitary pars intermedia in aged horses. 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 ...
Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants. 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...
Nitration and increased alpha-synuclein expression associated with dopaminergic neurodegeneration in equine pituitary pars intermedia dysfunction. 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...
Pituitary pars intermedia dysfunction: equine Cushing’s disease. 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...
Evaluation of pituitary gland anatomy and histopathologic findings in clinically normal horses and horses and ponies with pituitary pars intermedia adenoma. 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,...
Effects of season and sample handling on measurement of plasma alpha-melanocyte-stimulating hormone concentrations in horses and ponies. 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 ...
Serum insulin concentrations in horses with equine Cushing’s syndrome: response to a cortisol inhibitor and prognostic value. 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, ...
Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with equine Cushing’s disease. 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,...
Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitis. 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...
Efficacy of trilostane for the treatment of equine Cushing’s syndrome. 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...
Demographic and clinical characteristics of geriatric horses: 467 cases (1989-1999). 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...