Systemic and pituitary pars intermedia antioxidant capacity associated with pars intermedia oxidative stress and dysfunction in horses

OBJECTIVE: 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. SAMPLE POPULATION: 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. PROCEDURES: Total glutathione, superoxide dismutase, and glutathione peroxidase activities were determined in RBCs. Accumulation of a systemic marker of oxidative stress (3-nitrotyrosine) was assessed in plasma and formalin-fixed, paraffin-embedded adrenal gland and substantia nigra tissues. Local antioxidants (total and manganese superoxide dismutase, glutathione peroxidase, and total glutathione) were measured in pars intermedia tissues. RESULTS: No significant differences existed in systemic antioxidant enzyme activity or accumulation of 3-nitrotyrosine between horses with PPID and control horses. In pituitary gland tissues, glutathione peroxidase activity was increased in horses with oxidative stress, whereas total glutathione concentration and superoxide dismutase activity remained unchanged. There was an age-associated decrease in manganese superoxide dismutase activity in the pars intermedia. CONCLUSIONS AND CLINICAL RELEVANCE: There was no evidence of systemic accumulation of oxidative stress markers or deficiencies in antioxidant capacity in horses with PPID, suggesting that these are unlikely to be major predisposing factors in the development of PPID. Manganese superoxide dismutase activity in the pars intermedia decreased significantly with increasing age. Role of an age-associated decrease in antioxidant capacity for the pars intermedia in the development of PPID in horses warrants further investigation.     

Agreement in histologic assessments of the pituitary pars intermedia in aged horses

OBJECTIVE: 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. PROCEDURE: 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 among pathologists and with antemortem diagnostic test results was calculated. RESULTS: Overall, only fair agreement was found among the pathologists as to which horses had histologic findings consistent with disease (mean +/- SE kappa value, 0.34 +/- 0.069). Interpretation of individual sections varied, with minimal agreement (4 or 5/7 pathologists) for 5 of 10 sections evaluated. Postmortem assessment was in agreement with an antemortem endocrine diagnostic test result 79% of the time. CONCLUSIONS AND CLINICAL RELEVANCE: Validation of antemortem diagnostic testing for PPID in horses often relies on the results of postmortem histologic evaluation. The lack of consensus in histologic interpretation of pituitary glands from aged horses with mild clinical signs in our study indicates that postmortem histologic evaluation of pituitary glands is an inappropriate standard in validation of antemortem diagnostic tests for detection of early PPID. Caution should be used when interpreting diagnostic test results in horses in which early PPID is suspected.     

Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia

OBJECTIVE: 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). DESIGN: Prospective case series. ANIMALS: 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. PROCEDURES: ACTH concentrations prior to and after administration of TRH were measured 61 times in 48 horses. Results of the DST (cortisol response) were compared with those of the TRH test in 29 horses. Thirty-three horses (24 with no clinical signs of PPID, 5 with clinical signs of PPID, and 4 with equivocal clinical signs of PPID) were euthanized and necropsied and their pituitary glands evaluated. RESULTS: ACTH concentrations increased in all horses, but magnitude and duration of increase were significantly higher in horses with PPID. Endogenous ACTH concentrations were influenced by season. The ACTH baseline concentrations and response to TRH were not correlated with results of the DST. Results of DST were abnormal only in clinically abnormal horses or those with pars intermedia hyperplasia, but were within reference range in 17 of 26 tests in these horses. CONCLUSIONS AND CLINICAL RELEVANCE: The ACTH response to TRH is a useful test for diagnosis of pituitary gland hyperplasia, particularly in horses in which baseline ACTH concentrations are within reference range. The DST was specific but not sensitive and was inconsistent for individuals, and results often did not agree with the TRH test response.     

Comparison of Insulin and Glucose Metabolism in Horses with Pituitary Pars Intermedia Dysfunction Treated Versus Not Treated with Pergolide

Equine pituitary pars intermedia dysfunction (PPID) is known to alter glucose/insulin metabolism. This study evaluated changes in parameters relating to glucose/insulin metabolism and determined whether there is a difference between pergolide-treated and untreated animals. We hypothesized that glucose/insulin dynamics in PPID horses receiving pergolide would be different than those in untreated horses. A total of 38 horses with diagnoses of PPID were included in the study (average age: 24 years). A total of 25 horses were untreated; 13 horses were treated with pergolide (>3 months). Parameters relating to glucose/insulin metabolism were determined in all horses, as follows: adrenocorticotropin-releasing hormone (ACTH), insulin, fructosamine, triglyceride, glucose, modified insulin-to-glucose ratio (MIRG), and reciprocal of the square root of insulin (RISQI). A combined glucose-insulin test (CGIT) was performed in 23 horses as not all owners agreed to the testing. Treated animals showed a tendency to have lower ACTH, but results were not significant. All animals had fructosamine levels exceeding reference values (mean value 314 ± 32 μmol/L; reference range: <280 μmol/L). There were no statistically significant differences between insulin, glucose, ACTH, triglycerides concentrations, RISQI/MIRG calculations, and CGIT results of pergolide-treated PPID and those of untreated horses. Five horses (13.2%) had combined hyperglycemia/hyperinsulinemia, whereas 7 horses (18.4%) displayed hyperglycemia, and 3 horses (7.9%) showed hyperinsulinemia alone. Forty percent of the horses with altered glucose/insulin metabolism were treated with pergolide. Based on RISQI and MIRG calculations, 19 animals displayed changes in glucose/insulin metabolism. Fourteen of twenty-three horses (61%) showed signs of insulin resistance in CGIT results. In conclusion, PPID horses frequently show alterations in glucose/insulin metabolism, but no significant differences were found between treated and untreated animals. Changes in insulin/glucose dynamics may not be a useful indicator of response to pergolide treatment.     

Suspensory ligament degeneration associated with pituitary pars intermedia dysfunction in horses

In older horses, pituitary pars intermedia dysfunction (PPID) and suspensory ligament (SL) degeneration are common. The aim of the present study was to identify histopathological changes in the SL in horses with PPID. SLs of four horses with clinical signs of PPID (17–26 years of age) were compared with SLs from four old horses (18–31 years of age) and three young horses (4–9 years of age). In horses with PPID, there was reduced longitudinal arrangement of collagen fibres in SLs, along with inclusions of cartilage, extracellular matrix and haemorrhage, as well as significant proteoglycan accumulations between SL fibres. These changes are similar to the degeneration of connective tissues in Peruvian Paso horses with SL degeneration and in humans with Cushing's disease or after long term high dose corticosteroid treatments. These findings indicate an association between degeneration of the SL and PPID.     

Large pituitary adenoma in an 8‐year‐old Arabian stallion

An 8‐year‐old Arabian stallion weighing 361 kg presented to Louisiana State University Veterinary Teaching Hospital with a 3‐month history of weight loss, exercise intolerance, long hair coat and recent history of seizures and aimless wandering in the pasture. An initial presumptive diagnosis of pituitary pars intermedia dysfunction (PPID) was made based on clinical signs. The initial examination revealed weight loss and loss of body condition (BCS 3/9), hypertrichosis, muscle wasting and reluctance to move when prompted. A neurological examination revealed dull mentation with no evidence of proprioceptive deficits in the limbs. Mild hyperglycaemia and a stress leucogram were noted on initial biochemical panel and haematology, respectively. Plasma adrenocorticotrophic hormone (ACTH) concentrations before and after thyrotropin releasing hormone (TRH) stimulation were markedly increased. Rapid slice computed tomography (CT) scan of the head before and after contrast revealed a large mass in the region of the pituitary gland suggestive of macroadenoma causing PPID. Prior to imaging, treatment consisted of supportive nursing care. Due to size of the pituitary gland (measuring 4.6 × 4.6 × 3.8 cm) and the presence of seizure‐like activity and dull mentation, the stallion was subjected to euthanasia. A necropsy was not performed. Pituitary macroadenomas in horses affected with PPID, who show neurological signs such as seizure‐like activity, dull mentation and aimless wandering, might have a poor prognosis and treatment with pergolide mesylate might not reduce pituitary gland size or relieve clinical signs. A CT scan is indicated in horses with neurological signs suspected of PPID to further evaluate pituitary gland size and surrounding structures and rule out other causes to better assess prognosis.     

Association of Season and Pasture Grazing with Blood Hormone and Metabolite Concentrations in Horses with Presumed Pituitary Pars Intermedia Dysfunction

Background: Pituitary pars intermedia dysfunction (PPID) is a risk factor for pasture‐associated laminitis, which follows a seasonal pattern. Hypothesis: Hormonal responses to season differ between PPID and unaffected horses. Animals: Seventeen horses aged 8–30 years (14 horses ≥ 20 years of age). Methods: Longitudinal observational study. Blood was collected monthly from August 2007 until July 2008 after pasture grazing and again after overnight stall confinement. Blood hormone and metabolite concentrations were measured and pasture grass samples were analyzed to determine carbohydrate content. Analysis of variance analysis for repeated measures was performed. Results: Mean ACTH concentrations varied significantly over time (P < .001), with higher concentrations detected in August, September, and October compared with November–April. Pasture × time effects were detected for glucose and insulin concentrations, with peaks observed in September. Horses were retrospectively allocated to PPID (n = 8) and control (n = 9) groups on the basis of plasma ACTH concentrations. Changes in insulin concentrations over time differed in the PPID group when compared with the control group. Insulin concentrations were positively correlated with grass carbohydrate composition. Conclusions and Clinical Importance: PPID did not affect the timing or duration of the seasonal increase in ACTH concentrations, but higher values were detected in affected horses. Insulin concentrations differed between groups, but hyperinsulinemia was rarely detected. Glucose and insulin concentrations peaked in September when horses were grazing on pasture, which could be relevant to the seasonal pattern of laminitis.     

Circannual variation in plasma adrenocorticotropic hormone concentrations in the UK in normal horses and ponies, and those with pituitary pars intermedia dysfunction

Reasons for performing study: Pituitary pars intermedia dysfunction (PPID) is a common endocrinopathy, frequently diagnosed via plasma adrenocorticotropic hormone (ACTH) concentrations. Seasonal variation in plasma ACTH concentrations has been described in normal horses prompting caution in diagnosing PPID at certain times of the year. The aims of this study were to determine appropriate reference intervals for equine plasma ACTH throughout the year; and to examine the circannual variation of plasma ACTH concentrations in PPID cases. Hypothesis: Plasma ACTH can be used as a test for PPID throughout the year with the use of appropriate reference intervals. Methods: Data for reference interval calculations were obtained from samples collected from inpatients of Liphook Equine Hospital (non‐PPID group, n = 156). Data from PPID cases (n = 941) were obtained from samples submitted to the Liphook Equine Hospital Laboratory from horses with a clinical suspicion of PPID found to have plasma ACTH concentrations greater than our upper reference interval for that time of year. Results: Upper limits for reference interval of plasma ACTH were 29 pg/ml between November and July and 47 pg/ml between August and October. Circannual variation in plasma ACTH occurred in both non‐PPID and PPID horses with the highest ACTH concentrations found between August and October in both groups (P<0.0001). The greatest difference between the 2 populations also occurred between August and October. Conclusions: Plasma ACTH can be used for the diagnosis and monitoring of PPID throughout the year with the use of appropriate reference intervals. These findings demonstrate an increase in pituitary gland secretory activity during the late summer and autumn in both normal and PPID cases.     

Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses

Background –  Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. Objective –  The aim of this study was to compare hair follicle stages in PPID‐affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID‐affected horses after 6 months of treatment with pergolide mesylate with those of control horses. Animals –  Eight PPID‐affected horses and four normal, age‐matched, control horses. Methods –  Skin biopsies were collected from the neck and rump of PPID‐affected and control horses. A diagnosis of PPID was established based on hair coat changes and supportive overnight dexamethasone suppression test results. Skin biopsies were repeated after 6 months of treatment with pergolide. The number of hair follicles in anagen (A) or telogen (T) was counted for each skin biopsy using transverse sections. Results –  Pretreatment biopsies had a greater percentage of A follicles (neck 96%, rump 95%) and a lower percentage of T follicles (neck 4%, rump 5%) in PPID‐affected horses than in control horses (A, neck 15%, rump 25%; and T, neck 85%, rump 75%). After treatment with pergolide, all PPID‐affected horses had improved shedding, and the percentages of A follicles (neck 69%, rump 70%) and T follicles (neck 31%, rump 30%) were not different from untreated control horses (A, neck 68%, rump 82%; and T, neck 32%, rump 18%). Conclusions –  These findings document that excessive hair growth (hypertrichosis) in PPID‐affected horses is due to persistence of hair follicles in A. Furthermore, treatment with pergolide improved shedding and reduced the percentage of A follicles in PPID‐affected horses.     

Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction

BACKGROUND: 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. HYPOTHESIS: 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. ANIMALS: Aged horses with PPID, healthy aged-matched controls, and adult controls (n = 14 per group). METHODS: Total leukocyte cytokine expression was determined by quantitative polymerase chain reaction (PCR), and tumor necrosis factor (TNF)-alpha plasma concentration was determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cell (PBMC) TNF-alpha response after endotoxin (lipopolysaccharide [LPS]) treatment was assessed by ELISA. RESULTS: Aged healthy horses had increased expression of interleukin (IL)-6, IL-8, and interferon-gamma as well as PBMC TNF-alpha release after LPS stimulation compared with healthy adult horses. In contrast, aged horses with PPID had increased IL-8 expression, but expression of other cytokines was similar to that of healthy adult horses, not age-matched controls. CONCLUSIONS AND CLINICAL IMPORTANCE: Aged horses show evidence of a proinflammatory state that may contribute to development of age-associated diseases. Horses with PPID have increased expression of IL-8, which may influence the ability of horses with PPID to respond to bacterial pathogens. The general decrease in proinflammatory cytokine expression observed in horses with PPID may be the outcome of high plasma concentrations of anti-inflammatory hormones.     

Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitis

OBJECTIVE: To determine prevalence and clinical features of pituitary pars intermedia dysfunction (PPID) in horses with laminitis. DESIGN: Case series. ANIMALS: 40 horses with laminitis. PROCEDURES: 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, treatment, outcome, and postmortem examination findings were recorded. RESULTS: Prevalence of PPID as defined by a single high plasma ACTH concentration was 70%. Median age of horses suspected of having PPID (n = 28) was 15.5 years, and median age of horses without PPID (12) was 14.5 years. Laminitis occurred most frequently in horses with and without suspected PPID during September and May, respectively. Chronic laminitis was significantly more common in horses suspected of having PPID. In horses suspected of having PPID, the most common physical examination findings included abnormal body fat distribution, bulging supraorbital fossae, and hirsutism. Five horses suspected of having PPID had no clinical abnormalities other than laminitis. Seventeen horses suspected of having PPID that were treated with pergolide survived, and 3 horses that were not treated survived. CONCLUSIONS AND CLINICAL RELEVANCE: Evidence of PPID is common among horses with laminitis in a primary-care ambulatory setting. Horses with laminitis may have PPID without other clinical signs commonly associated with the disease.     

Prevalence,risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses

Reasons for performing study: Equine pituitary pars intermedia dysfunction (PPID) is an ageing‐related neurodegenerative disorder. The prevalence and risk factors for PPID using seasonally adjusted basal adrenocorticotropic hormone (ACTH) concentrations in aged horses have not been previously reported. Objectives: To determine the prevalence, risk factors and clinical signs predictive for PPID in a population of horses aged ≥15 years in Queensland, Australia. Methods: Owner‐reported data was obtained using a postal questionnaire distributed to an equestrian group. A subgroup of surveyed owners were visited and a veterinary physical examination performed on all horses aged ≥15 years. Blood samples were analysed for basal plasma alpha melanocyte‐stimulating hormone (α‐MSH) and ACTH concentrations, routine haematology and selected biochemistry. Aged horses with elevations above seasonally adjusted cut‐off values for basal plasma ACTH were considered positive for PPID. Positive horses were compared with their aged counterparts to determine risk factors and clinical signs associated with PPID. Results: Pituitary pars intermedia dysfunction was prevalent in aged horses (21.2%) despite owners infrequently reporting it as a known or diagnosed disease or disorder. Numerous clinical or historical signs were associated with an increased risk of PPID in the univariable model, but only age (odds ratio (OR) 1.18; 95% confidence interval (CI) 1.11–1.25, P<0.001) and owner‐reported history of hirsutism (OR 7.80; 95% CI 3.67–16.57, P<0.001) remained in the final multivariable model. There were no routine haematological or biochemical variables supportive of a diagnosis of PPID. Conclusions and potential relevance: Pituitary pars intermedia dysfunction occurs commonly in aged horses despite under‐recognition by owners. The increased risk of PPID with age supports that this is an ageing associated condition. Aged horses with clinical or historical signs consistent with PPID, especially owner‐reported hirsutism (delayed shedding and/or long hair coat), should be tested and appropriate treatment instituted.     

The Influence of the Size,Age and Sex on the Computed Tomographic Measured Size of the Pituitary Gland in Normal Horses

The objective of this study was to examine the influence of the size, age and sex of the horse on the size of the pituitary gland and determine the possibility of using the pituitary gland height‐to‐brain area ratio (P:B ratio) to allow comparison of different sized and aged horses. Thirty‐two horses without pituitary pars inter‐media dysfunction that underwent a contrast‐enhanced computed tomographic (CT) examination were included in a cross‐sectional study. On the CT images, the pituitary gland height was measured and the P:B ratio was calculated. These measurements were correlated to the size, age and sex of the horses. The pituitary gland height was significantly associated with the size (P < 0.001) and the age (P < 0.001), but not with the sex (P = 0.40), of the horses. No significant association was found between the P:B ratio and the size (P = 0.25), the age (P = 0.06) or the sex (P = 0.25) of the horses. In conclusion, the pituitary gland size varies between different sized and aged horses. The use of the P:B ratio is a valuable metric for making comparisons between the pituitary glands of these horses.     

The Effect of Season on the Histologic and Histomorphometric Appearance of the Equine Pituitary Gland

The objective of this study was to determine the effect of season on the histologic and histomorphometric appearance of the normal equine pituitary gland. Pituitary glands were collected at necropsy from 121 horses throughout the year. Plasma was also collected from 59 of these horses before euthanasia. Hematoxylin and eosin stained median sagittal sections of each pituitary were evaluated and histologically graded by three pathologists. Histomorphometric analysis was performed on the same slides. Plasma α-melanocyte stimulating hormone was measured by radioimmunoassay in a subset of horses (n = 59). A total of 118 pituitary glands were included in the study after exclusions were made on the basis of the presence of pars intermedia (PI) adenomas (>5 mm). There was a positive correlation between PI hormone concentration (α-melanocyte stimulating hormone) and PI area. Pituitary gland measurements and grades from samples collected in the fall were compared with those collected in the nonfall months using t-test. The PI area, total pituitary area, and PI/total pituitary ratio were significantly greater in the fall compared with nonfall months (P < .0001, P < .01, P < .0001, respectively). Pituitary grades were also higher in the fall compared with nonfall months (P < .001). There was no seasonal difference in pars distalis or pars nervosa area. The results of this study show that the normal equine pituitary shows seasonal changes in appearance and size. These changes must be considered when using postmortem histologic evaluations in the diagnosis of pituitary pars intermedia dysfunction or for validation of antemortem diagnostic tests.     

How Does Cushing’s Disease Relate to Laminitis? Advances in Diagnosis and Treatment

The pathophysiology of pituitary pars intermedia dysfunction (PPID) and its connection to laminitis have been the focus of much recent research. This article reviews the pathophysiology, diagnostics, and treatments of PPID, as well as the proposed pathogenesis of laminitis in these horses. An increased understanding of the disease process, along with appropriate diagnosis and treatment, can often minimize the devastating laminitis often associated with PPID.     

Pituitary apoplexy-like disease in 4 dogs

BACKGROUND: Pituitary apoplexy in humans is a clinical syndrome resulting from sudden infarction, hemorrhage, or both in a normal or an adenomatous pituitary gland. OBJECTIVE: Describe a clinical syndrome in dogs similar to pituitary apoplexy in humans. ANIMALS: Four dogs exhibiting a sudden onset of neurologic signs. METHODS: A retrospective study was used, including clinical examination, computed tomography (CT), postmortem examination, and histopathology of the brain. Pituitary tissue from 3 of the dogs was subjected to immunocytochemistry. RESULTS: Four dogs (2 Mongrels, 1 Bordeaux Dog, and 1 Cocker Spaniel; median age, 11 years; median body weight, 20.5 kg) presented with acute neurologic signs including depression (n = 3), behavioral changes (n = 1), vision loss (n = 1), seizures (n = 1), and collapse (n = 1). CT disclosed suprasellar infarction, hemorrhage, or both associated with a pituitary macroadenoma in 3 dogs and a frank hemorrhage in a nonadenomatous pituitary gland in 1 dog. CT findings were correlated with postmortem findings, and pituitary apoplexy was confirmed by histopathology and immunocytochemistry of the pituitary tissue. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides histopathologic evidence of pituitary apoplexy in dogs. The results are relevant for future diagnosis and treatment of pituitary disease in dogs.     

The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and α-melanocyte-stimulating hormone plasma concentrations in horses

Background: Plasma α‐melanocyte‐stimulating hormone (α‐MSH) and adrenocorticotropin (ACTH) concentrations in horses vary with season, confounding diagnostic testing for pituitary pars intermedia dysfunction (PPID). Hypothesis: The goals of this study were to determine whether seasonal variation in plasma α‐MSH and ACTH concentrations in horses is influenced by geographic location, breed, or PPID. Animals: Healthy light breed horses residing in Florida, Massachusetts, and Finland (n = 12 per group); healthy Morgan horses (n = 13); healthy ponies (n = 9) and horses with PPID (n = 8). Methods: Monthly plasma α‐MSH and ACTH concentrations were measured by radioimmunoassay. Nonlinear regression analysis was used to estimate the time of peak hormone concentrations. Mean hormone concentrations in fall and nonfall months were compared. Results: The fall peak plasma α‐MSH concentration occurred earlier in horses residing at more northern locations. Mean seasonal α‐MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in horses living in more southern locations. Plasma ACTH but not α‐MSH concentrations were higher in Morgan horses compared with light breed horses from the same location. Hormone concentrations of ponies did not differ from those of horses during either season. Concentrations of both hormones were high in the fall compared with the spring in horses with PPID. Conclusions and Clinical Importance: These findings suggest geographic location of residence and breed may affect the onset, amplitude, or both of the seasonal peak of pars intermedia (PI) hormones and should be considered when performing diagnostic testing for PPID. Horses with PPID maintain seasonal regulation of PI hormone output.     

Circadian and circannual rhythms of cortisol,ACTH, and α-melanocyte-stimulating hormone in healthy horses

Cosinor analysis was used to evaluate whether pituitary and adrenal hormones exhibit circadian rhythmicity in horses. The effect of season and animal age on their respective rhythms was also determined. In addition, the usefulness of evaluating cortisol rhythmicity for the diagnosis of pituitary pars intermedia dysfunction (PPID) was assessed. Serum cortisol concentrations (P < 0.01), but not plasma ACTH or α-melanocyte-stimulating hormone (α-MSH), showed a significant circadian periodicity in horses. An effect of season on hormone concentration was observed with plasma ACTH and α-MSH concentration greater in the fall and cortisol concentration greater in the spring (P < 0.001). Age did not affect cortisol rhythm, but it did blunt the variation in cortisol concentration in horses, similar to what has been previously reported to occur in aged people and dogs. In addition, our results suggest that clinically and diagnostically normal, non–PPID-affected horses commonly have a loss of cortisol diurnal rhythm. Therefore, measurement of circadian rhythm is not an appropriate diagnostic test for PPID.     

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 endogenous adrenocorticotrophic hormone (eACTH) by PI melanotrophs. To test this, plasma eACTH concentration was determined in horses with or without clinical signs of PPID at 0, 4, and 8 hours after oral administration of 3.3 mg domperidone/kg. Pituitary glands were evaluated postmortem by histologic grading and morphometry. In the 33 horses, median age, plasma ACTH concentration 8 hours after domperidone, and PI area in median sagittal sections were associated with histologic grade as follows: pituitary grade 1 (normal), n = 3, 7.5 years, 20.0 pg/ml, 0.16 cm(2); grade 2 (focal hypertrophy or hyperplasia), n = 9, 14.5 years, 27.1 pg/ml, 0.27 cm(2); grade 3 (diffuse adenomatous hyperplasia), n = 5, 21.0 years, 64.4 pg/ml, 0.48 cm(2); grade 4 (microadenomas), n = 12, 23.3 years, 128.0 pg/ml, 0.87 cm(2); grade 5 (adenoma), n = 4, 24.9 years, 720.5 pg/ml, 2.1 cm(2). Results suggest that horses with pituitary histologic grade > or =3 respond to domperidone with increased plasma ACTH concentration.     

Antidiuretic response of a horse affected with pituitary pars intermedia dysfunction to desmopressin acetate

Central diabetes insipidus (DI) was diagnosed in a 20‐year‐old American Quarter Horse gelding that was concomitantly affected with pituitary pars intermedia dysfunction (PPID). The diagnosis of DI was supported by a positive response to administered desmopressin acetate. Diagnosis of PPID was supported by physical appearance and elevated plasma adrenocorticotropic hormone concentration following domperidone administration. The horse's physical condition improved following treatment with pergolide but long‐term treatment with desmopressin was not undertaken and severe polyuria and polydipsia persisted. Desmopressin acetate appears to be useful for the diagnosis of DI in mature horses concomitantly affected with PPID.