Pituitary Pars Intermedia Dysfunction Research Articles

Development and Evaluation of a Muscle Atrophy Scoring System (MASS) for Horses

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 region (ICC = 0.29). Due to this low agreement, the abdominal region was excluded from further analysis. Associations between muscle atrophy scores and age, pituitary pars intermedia dysfunction (PPID) status, and body composition indicators, including weight and estimated fat-free mass (FFM), were examined. Weight was inversely associated with neck, back and hind muscle atrophy scores (β = -0.008, β = -0.008, β = -0.009, respectively; all P <0.001), but estimated FFM was not associated with muscle atrophy scores at any region (P >0.05). Age was positively related to neck (β = 0.030, P <0.01), back (β = 0.037, P <0.001) and hind (β = 0.040, P <0.001) muscle atrophy scores. PPID-positive horses (n = 4) had higher muscle atrophy scores than PPID-negative horses (n = 23), even after adjusting for age (P <0.05). This data suggests that neck, back and hind region evaluations by individual raters likely have acceptable reliability. In addition, these findings support further evaluation of the potential benefits of the MASS to identify and monitor muscle atrophy in horses.

Equine multinodular pulmonary fibrosis in a Thoroughbred with pituitary pars intermedia dysfunction

Equine multinodular pulmonary fibrosis in a Thoroughbred with pituitary pars intermedia dysfunction

Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy

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 of α-syn isolated from PPID-afflicted horses. Next, detection of α-syn fibrils in pars intermedia via transmission electron microscopy (TEM) was exclusive to PPID-afflicted horses. A bank of fragment peptides was designed to further characterize equine α-syn misfolding. Region 62–87 of equine and human α-syn peptides was found to be most prone to aggregation according to Tango bioinformatic program and kinetics of aggregation via a thioflavin T fluorescence assay. In both species, fragment peptide 62–87 is capable of generating mature fibrils as demonstrated by TEM. The combined animal, bioinformatic, and biophysical studies provide evidence that equine α-syn is misfolded in PPID horses.

Impact of blue light therapy on plasma adrenocorticotropic hormone (ACTH) and hypertrichosis in horses with pituitary pars intermedia dysfunction

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 (n = 10) or the treatment (blue light therapy) group (n = 8) based on age and clinical history, which included the results of multiple endocrine tests. Consistent daylength of approximately 14.5 h was maintained for the treated horses from July 15 through approximately late October via the extension of natural daylength using wearable masks that provided short wavelength blue light (465 nm) to 1 eye. The control group was exposed to only the natural photoperiod during this time. All horses were housed on the same farm and remained on pasture for the duration of the study. On Day 0, thyrotropin-releasing hormone (TRH) stimulation tests were performed to confirm PPID status; there were no differences between the 2 groups in resting plasma ACTH or plasma ACTH at 10 min after TRH administration. To determine an effect of treatment on ACTH, blood was collected via jugular venipuncture for measurement of ACTH at sequential timepoints over a 16-h period in mid-October. Hair weights were also assessed throughout the study. No differences in resting plasma ACTH were observed between the 2 groups across the seasonal analysis (July and October) or during the 16-h testing. The PPID horses receiving blue light therapy had lighter hair weights compared to the PPID control horses. These results suggest that blue light therapy does not alter ACTH concentrations but could potentially be used as an additional management tool for hypertrichosis in PPID horses. Manipulation of the photoperiod using blue light therapy did not affect seasonal changes in ACTH in this study.

Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares.

BackgroundPituitary 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.Hypothesis/ObjectiveBroodmares with infertility of unknown etiology were screened for PPID using baseline endogenous plasma ACTH concentrations, and its relationship with subsequent reproductive performance was analyzed.AnimalsSixty‐seven Thoroughbred broodmares.MethodsAdrenocorticotropic hormone concentrations were measured in autumn. The broodmares were divided into 3 groups based on endogenous plasma ACTH concentration (low, <50 pg/mL; intermediate 50‐100 pg/mL; and high >100 pg/mL) as recommended by the Equine Endocrinology Group. We compared these results with those of other blood tests, clinical examinations, subsequent conception, and frequency of normal delivery.ResultsThe numbers of horses per group (percentage) were 22 (32.8%), 20 (29.9%), and 25 (37.3%). The mean ± SD ages (years) were 11.1 ± 3.4, 12.1 ± 4.5, and 13.0 ± 4.3, with no significant difference among groups. Mean ± SD plasma cortisol concentrations (μg/dL) were 4.0 ± 1.6, 7.1 ± 1.4, and 7.6 ± 1.9, with the intermediate and high ACTH groups having significantly higher results than the low ACTH group (P < .001). Conception rates were 77.3%, 89.5%, and 56.5% and normal delivery rates were 77.2%, 84.2%, and 43.5% with the percentage of each significantly lower in the high ACTH group (P = .02, P = .008, respectively).Conclusions and Clinical ImportanceThe study group of infertile broodmares may include horses with PPID. The reproductive performance of the high ACTH group was significantly lower than the other groups. Early diagnosis and treatment of infertile broodmares by screening plasma ACTH concentrations could help improve reproductive performance.

Potential Neuroprotection for Equine Pituitary Pars Intermedia Dysfunction

Cushing's disease, known as pituitary pars intermedia dysfunction (PPID), is the most commonly diagnosed equine endocrinopathy. Compelling evidence suggests that alpha-synuclein, an abundant neuronal protein, can acquire a neurotoxic feature that kills dopamine secreting nerve cells in horse afflicted with PPID. Horseswith PPID have higher levels ofalpha-synuclein in the dopaminergic nerve terminals withinthe pars intermedia of the pituitary gland compared withhealthy horses. Using protein extracts from pituitary glands of horses with PPID, biophysical assays, and bioinformatic analysis, we have identified that equine alpha-synuclein has high propensity to convert (misfold and aggregate) into this toxic form. Our drug discovery lab focusses on identifying and designing small molecules to impede the formation of intermediate species and fibrils. Over the last decades, natural products have emerged as neuroprotective agents for chronic neurodegenerative diseases. We hypothesize that a natural product such as resveratrol locks equine alpha-synuclein molecules into a conformation unable to form cytotoxic oligomers and fibrils, thereby conferring cytoprotection. Most recently, we have identified the region 62-86 in the equine alpha-synuclein that is highly prone to convert into a toxic conformation. Fragment 62-86 is part of the non-amyloid-β component (NAC), a hydrophobic region that may contribute to alpha-synuclein oligomerization. The carboxy-terminal region (90-140) exhibits the lowest aggregation score. This region is intrinsically disordered and may contribute minimally to the aggregation. We conducted a pilot screening with silibinin and resveratrol (both flavonoids and natural products) on the different equine and human alpha-synuclein fragment peptides with thioflavin T fluorescence (ThT) assay. Resveratrol decreased relative ThT fluorescence of equine alpha-synuclein fragment 62-86 by ~70%. Treating equine alpha-synuclein fragment 62-86 with resveratrol reduced the number of alpha-synuclein fibrils as assessed by transmission electron microscopy. This project will set the stage to move into a lead optimization program and underscore the value of equine alpha-synuclein in PPID drug discovery.

8 Suspected presence of macroprolactin in the plasma of horses and ponies

Prolactin is a peptide hormone that plays a role in various physiological functions and its production is influenced by several factors (thyrotropin-releasing hormone, dopamine, season, meal feeding or physiological state such as lactation). Plasma levels help understand reproductive physiology; but may also be a useful indicator of dopamine production at a central level (connection between the hypothalamus and pituitary gland). In human medicine, when prolactin is measured using sandwich immunometric methodologies in automated analysers, hyperprolactinemia diagnosis may be confounded by the presence of a high molecular mass prolactin/IgG autoantibody complex termed macroprolactin, which does not have biological effects. Macroprolactinaemia has not previously been described in horses. Previously equine prolactin has been measured by radioimmunoassay (RIA) analysis; however, more rapid ELISA assays are now available without the radioactive tracer health and safety considerations. In this study, prolactin was measured in plasma from 20 normal horses and 20 horses with pituitary pars intermedia dysfunction, using a commercial ELISA assay (Biorbyt, UK). Surprisingly, while most showed values below 100 ng/mL, 13 appeared to have extremely high concentrations, well in excess of the upper limit of the standard curve at 1000 ng/mL. There was no significant association of this finding with disease category, breed, sex or age. To determine whether the presence of macroprolactin could be causing these aberrant values, a polyethyleneglycol (PEG) precipitation step was introduced, as previously shown in humans, to remove the macroprolactin while leaving the monomeric form in solution. After the addition of PEG and centrifugation to precipitate out macroprolactin, the supernatant with the unprecipitated prolactin was tested and compared with unprecipitated samples from the same individuals. PEG precipitation resulted in a reduction in prolactin values by more than 99% in those with apparent hyperprolactinaemia (to below 200 ng/mL in all cases except one at 243 ng/mL). In the other samples the values were reduced from 67.4 ± 9.9ng/ml to 10.6 ± 0.7ng/ml (approximately 75% reduction). Although this data is preliminary and more validation work is necessary, these findings are consistent with macroprolactin being detected by the ELISA assay in these individual horses. While it may be possible to validate the ELISA assay for measuring prolactin in equine plasma, a PEG precipitation step is required to remove this interfering substance. Further research is needed to confirm the presence and size characteristics of this macroprolactin complex in equine plasma.

Pergolide dosing compliance and factors affecting the laboratory control of equine pituitary pars intermedia dysfunction.

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) or not. In total, 110 animals were included. The majority (85%) were ≥16 years (mean ± SD 19.8 ± 4.4 years); the most common breeds were Cob (18%), Thoroughbred (16%) and Welsh (15%); 37% were female and 63% male. Overall, 48% were compliant and 52% non-compliant. There was no significant effect of compliance on laboratory control. Of those that were compliant, 74% were controlled, while 67% of non-compliant animals were controlled. Univariable analysis revealed a significant (p < 0.001) effect of age and breed on compliance and control, and of sex on control. On multivariable analysis, only age (compliance) and breed (compliance and control) were retained in the final model. Only half of animals received the recommended pergolide dose; however, this did not affect laboratory control of PPID.

Pituitary Pars Intermedia Dysfunction with Laminitis in a Horse

Pituitary Pars Intermedia Dysfunction with Laminitis in a Horse

Markers of muscle atrophy and impact of treatment with pergolide in horses with pituitary pars intermedia dysfunction and muscle atrophy

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 atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis (muscle atrophy F- box/atrogin 1 [MAFbx1], muscle RING finger 1 [MuRF1], Bcl2/adenovirus EIV 19kD interacting protein 3 [Bnip3], and microtubule-associated light chain 3 [LC3]) were compared between PPID and control horses. PPID horses were treated for 12 weeks with either pergolide or placebo. Dose of pergolide was adjusted based upon monthly measurement of adrenocorticotropin, and markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis were compared after 12 weeks of treatment. Horses with PPID exhibited increased transcript abundance of MuRF1 (P= 0.04) compared to control. However, no difference was observed in transcript abundance of markers of proteolysis with treatment (P ≥ 0.25). Pergolide treated horses lost weight (P = 0.02) and improved fasting insulin (P = 0.02), while placebo treated horses gained weight and rump fat thickness (P = 0.02). Findings from this study suggest that treatment with pergolide may promote weight loss and improve insulin regulation in horses with PPID, but does not impact muscle mass or markers of muscle proteolysis.

Investigation of innate immune function in adult and geriatric horses

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 function and body weight were measured to assess any potential impacts of ACTH, insulin, or body weight on immune function; none of the horses had pituitary pars intermedia dysfunction. The geriatric horse group had lower concentrations of plasma myeloperoxidase (P = 0.0459) and lower absolute monocyte counts (P = 0.0477); however, the difference in monocyte counts was no longer significant after outliers were removed. Additionally, only two significant differences in cytokine/receptor expression in whole blood were observed. Compared with adult horses, the geriatric horses had increased TNFα expression after in vitro stimulation with heat-inactivated R. equi (P = 0.0224) and had decreased IL-17α expression after PMA/ionomycin stimulation when one outlier was excluded (P = 0.0334). These changes may represent a compensatory mechanism by which geriatric horses could ensure adequate immune responses despite potentially dysfunctional neutrophil activity and/or decreased monocyte counts. Aging may influence equine innate immune function, and additional research is warranted to confirm and further explore these findings.

Laser Acupuncture Treatment of Equine Cushing’s Syndrome

Equine Cushing’s syndrome (ECS), or pituitary pars intermedia dysfunction (PPID), is a chronic progressive pituitary disease that occurs almost exclusively in older horses and ponies. Management of this chronic disease can be difficult, particularly in individuals that don’t respond to the medication, pergolide, which is one of the only effective treatments at this time. The use of low-level impulse lasers (LLL) to treat ECS are introduced in this paper. They have been applied focally to stimulate acupoints (laser acupuncture) and topically over wounds, joints and other tissues to increase circulation and promote healing. Laser acupuncture therapy is an effective treatment method, which is relatively easy to learn and apply. It is an extremely effective therapy for numerous chronic degenerative diseases. The cases presented in this paper are a small sample of well over 30 ECS patients that have been successfully treated with laser acupuncture. Treatment protocols are presented for optimum laser acupuncture therapy along with a review of laser mechanism of action and appropriate selection. Treatment usually takes between 6 weeks and 3 months, and it appears that even horses that have had chronic disease for years can still have positive clinical outcomes.

Equine pituitary pars intermedia dysfunction: Identifying research priorities for diagnosis, treatment and prognosis through a priority setting partnership.

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 about the diagnosis, treatment and prognosis of PPID were gathered via an online survey targeting veterinary surgeons and horse owners with experience of PPID. Thematic analysis was used to form a longlist of collated indicative research questions (CIRQs), defined by the JLA as true ‘evidence uncertainties’ when not answered by a published, clinically relevant, up-to-date systematic review. In an interim prioritisation survey, questions were ranked by weighted scores creating a shortlist of 25 that were taken forward to the PSP workshop, where participants reached a consensus on the top 10. Useable responses containing ≥1 question were received from 524 respondents (92.6% owners, n = 485; 7.4% veterinary surgeons, n = 39). After screening for relevance, 1,260 individual questions were included in thematic analysis, resulting in 47 CIRQs. Interim prioritisation votes for the CIRQs were received from 360 respondents. The top 10 questions prioritised at the PSP workshop focused on long-term prognosis, diagnostic accuracy, efficacy of pergolide treatment, alternative treatment/management strategies and potential treatment options for poor responders to pergolide. The quantity of questions generated indicates an extensive number of uncertainties regarding the diagnosis, treatment and prognosis of PPID. The top 10 research questions will help to inform key areas for evidence synthesis and knowledge translation, and to direct future research into areas most important to end users involved in caring for and treating animals with PPID.

Preliminary study on the effects of pergolide on left ventricular function in the horses with pituitary pars intermedia dysfunction.

BackgroundPituitary 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.ObjectivesTo determine whether pergolide induces valvular disease in horses or affects the cardiac function.MethodsStandard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in horses with diagnosed PPID based on adrenocorticotropic hormone dosage. Measurements taken in horses treated with pergolide were compared with those from untreated horses with nonparametric t-tests. Furthermore, measurements from follow-up examinations performed at least three months after the initial exam were compared with a Wilcoxon signed rank test for repeated measurements in each group.ResultsTwenty-three horses were included. None of the 12 horses under treatment developed valvular regurgitation. Furthermore, no differences in the measurements of the left ventricular systolic or diastolic function could be seen between the group of horses with treatment and those without treatment. Measurements taken in the follow-up exam did not differ compared to those taken in the initial exam in both groups.ConclusionsNo changes of the left ventricular function assessed by TDE and STE could be shown in a small population of horses with confirmed PPID. Treatment with pergolide did not affect the ventricular function nor induce valvular disease.

Clinical care of the geriatric horse

Background: Geriatric horses account for a significant proportion of the UK horse population and therefore age‐related conditions are commonly encountered in equine practice.Aim of the article: This review aims to provide an overview of the practical approach to managing osteoarthritis, pituitary pars intermedia dysfunction, dental disease, weight loss and nutrition and colic in geriatric horses.

Circulating microRNAs in insulin resistant horses and ponies

Insulin resistance is a prevalent disorder among horses and is associated with abnormal adiposity, laminitis, equine metabolic syndrome, and pituitary pars intermedia dysfunction. The processes leading to equine insulin resistance and associated conditions remain subject for study. MicroRNAs (miRNAs) are involved in regulation of many biological processes and diseases. The current study aimed to investigate the circulating miRNA profile of insulin resistant horses and ponies. It was hypothesized that insulin resistant horses would have a different circulating miRNA profile compared to healthy ones. 12 Thoroughbred/ Thoroughbred-cross and 12 Welsh/Dartmoor non-pregnant mares were evaluated for insulin sensitivity using frequent sampling intravenous glucose tolerance test (FSIGTT). Serum samples were collected for miRNA profiling through RT-qPCR analysis. Horses and ponies were divided into insulin sensitive (IS) or insulin resistant (IR) groups and their miRNA profiles compared. Results demonstrated that 13 miRNAs were differently expressed between IR and IS horses, 15 between IR and IS ponies, 17 between horses and ponies, and 10 between IR and IS animals (horses and ponies combined) (p<0.05). Finally, 8 miRNAs were proposed as potential regulators of equine insulin resistance. miRNA profiling is a potential tool to evaluate insulin resistance and associated conditions.

Management of Pituitary Pars Intermedia Dysfunction in Practice: A Clinical Audit

Management of Pituitary Pars Intermedia Dysfunction in Practice: A Clinical Audit

Diagnostic Process in a Crioulo Horse with Cushing’s Syndrome

Background: Equine pituitary pars intermedia dysfunction, also known as equine Cushing’s syndrome, is a neurodegenerative disease. An important risk factor for Cushing’s is advanced aging and it is the most common endocrine disorder in older horses. The prevalence in horses aged over 10 and 15 years is reported as 9.3% and 21%, respectively. Due to the slow progressive nature of the disease, seasonal variation in hormone output and overlapping endocrine response to other events, accurate diagnosis is challenging. The diagnosis requires the combination of anamnesis, clinical signs, in addition to laboratory tests results. This study aimed to report Cushing’s syndrome in a Crioulo breed horse focusing on diagnostic methods.Case: A 13-year-old male Crioulo breed, orchiectomized, was attended at the Universidade de Passo Fundo (UPF), in Passo Fundo, RS, Brazil. The owner reported that the animal had progressive weight loss and coat abnormal growth, with curly appearance. From visual inspection, body condition score was 4 (1-9) bulging abdomen was noticed, hirsutism, depression and lethargy. Also, there was a large neoplastic mass on the left side of gluteal region. Later, this mass was classified in histopathological examination as a fibroblastic sarcoid and was treated. The animal presented physical parameters within the physiological limits of the specie. Normochromic normocytic anemia and neutrophilic leukocytosis were reported in the hematologic evaluation. In coproparasitological examination, there were 300 eggs per gram of feaces. Hyperadrenocorticism was suspected in the clinical examination and dexamethasone suppression test was performed to confirm the fact. Basal serum was collected at 17 h (M0) and subsequently 40 µg/kg of dexamethasone was administered intramuscularly. Serum samples were taken after 15 (M15) and 19 (M19) h, resulting in cortisol levels of 1.7 and 1.8 μg/dL, respectively. The M15 and M19 results were above reference values for horses (below 1 μg/dL). Combination of information gathered from anamnesis, clinical examination and dexamethasone suppression test resulted in the definitive diagnosis of hyperadrenocorticism, also known as Cushing’s syndrome. Paliative treatment included shearing all over the body and vitamin supplementation.Discussion: In animals without obvious clinical signs, Cushing's syndrome diagnosis is challenging. The most unique and specific clinical signs are the development of abnormal hair coat, mainly hirsutism, delayed or incomplete shedding, and in aged horse, lightening of coat color. The mechanistic cause of these signs is still barely understood. Cushing's is a collection of syndromes each with a unique set of clinical signs and hormone profiles, which varies according to each individual. Complementary examinations are extremely important and endocrine tests are highly recommended in addition to suggestive findings. However, despite the variety of existing tests, false negatives or false positives can frequently happen. Dexamethasone suppression test is considered the gold standard, well validated, practical and low cost for the diagnosis of this disease. In the present report, the combination of anamnesis (13 years old, weight loss, and abnormal coat), clinical exam (hirsutism) and dexamethasone suppression test (over 1 μg/dL of cortisol 15 h and 19 h after dexamethasone administration) resulted in the definitive diagnosis of Cushing’s syndrome. Measurements of plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH), thyrotropin releasing hormone (TRH) stimulation test, serum insulin concentration and necropsy are other available tests. History, clinical signs and test results are important to achieve the definitive diagnoses, and when possible, it is advisable to perform post-mortem evaluation of the pituitary gland.

Clinical implications of using adrenocorticotropic hormone diagnostic cutoffs or reference intervals to diagnose pituitary pars intermedia dysfunction in mature horses.

BackgroundDiagnosis of pituitary pars intermedia dysfunction (PPID) is problematic because of large variations in ACTH concentrations.Hypothesis/ObjectivesCompare 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.AnimalsOne hundred six mature horses: 72 control cases and 34 PPID cases.MethodsProspective case‐controlled study. Horses underwent monthly TRH stimulation tests. Diagnostic cutoff values were determined monthly by receiver operating characteristic curves using the Youden index. Reference intervals were determined monthly by a robust method. For each case age, sex and body condition score (BCS) were recorded.ResultsBaseline ACTH concentrations varied by month (P < .001) with significant “month × age” (P = .003), “month × sex” (P = .003), and “month × BCS” (P = .007) effects. Baseline ACTH concentrations were accurate to diagnose PPID (0.91 ± 0.06) with DCOVs increasing the test sensitivity (0.61 ± 0.21 to 0.87 ± 0.05, P = .002) and RI increasing test specificity (0.85 ± 0.12 to 0.98 ± 0.01, P = .01). Thyrotropin‐releasing hormone stimulation improved test accuracy (0.91 ± 0.06 to 0.97 ± 0.03, P = .004).Conclusions and Clinical ImportanceACTH concentrations follow a circannual rhythm and vary with physiological factors. As using DCOVs increases the ability to detect mild cases and using RI decreases the risk of unnecessary treatments, ACTH concentrations should be interpreted within a specific clinical context. The TRH stimulation test improves the diagnosis of PPID.

Pituitary Pars Intermedia Dysfunction and Metabolic Syndrome in Donkeys.

Simple SummaryDonkeys are one of the six species of the equid family. Even though they may look similar to horses, there are optical, behavioral, and physiological differences between the two species. The most important endocrine diseases in horses (equine metabolic syndrome and pituitary pars intermedia dysfunction: PPID) also exist in donkeys. The key symptoms of asinine metabolic syndrome (AMS), similar to horses, are obesity, insulin dysregulation, and laminitis. It can be diagnosed with either basal glucose and insulin concentration or dynamic tests. The intravenous glucose tolerance test and the combined glucose insulin tolerance test were evaluated for donkeys. The therapy of AMS is aimed at weight and exercise management. Donkeys suffering from PPID are often laminitic. Other authors have reported on hypertrichosis as a cardinal sign. Donkey-specific differences in shedding compared to horses have to be considered. The PPID can be diagnosed with donkey-specific reference values or dynamic testing. The dexamethasone suppression test, the thyrotropin releasing hormone (TRH) test, and the combined dexamethasone suppression/TRH test were evaluated for donkeys.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 similar to horses. Donkey-specific reference ranges for insulin and glucose have been evaluated previously. Examinations regarding dynamic testing revealed differences in the intravenous glucose tolerance test and the combined insulin tolerance test compared to horses. The therapy of AMS is based mainly on weight loss and exercise. There are conflicting data regarding the incidence of PPID in donkeys. Laminitis and hypertrichosis were described as the main clinical signs. Species-specific and seasonal reference ranges were defined to diagnose PPID in donkeys. Furthermore, the dexamethasone suppression test, the thyrotropin releasing hormone (TRH) test and the combined dexamethasone suppression/TRH test were evaluated. Pergolide is commonly recommended for treatment.