Evaluation of the effects of age and pituitary pars intermedia dysfunction on corneal sensitivity in horses.

OBJECTIVE: To determine effects of age and pituitary pars intermedia dysfunction (PPID) on corneal sensitivity in horses. ANIMALS: 20 adult horses allocated into 3 groups (PPID group, old [> 15 years old] horses with PPID [n = 5]; old group, old [> 15 years old] horses without PPID [9]; and young group, young [≤ 10 years old] horses without PPID [6]). All horses with PPID had hirsutism and abnormal fat deposition or laminitis; none of the old or young horses had hirsutism, abnormal fat deposition, or laminitis. PROCEDURES: A Cochet-Bonnet aesthesiometer was used to measure the corneal touch threshold (CTT) in both eyes of each horse. The nylon monofilament was applied at a maximum length of 60 mm to the central region of the cornea and length was decreased by 5-mm increments until a consistent blink response was elicited. Tear production was assessed in all eyes via the Shirmer tear test (STT). RESULTS: Mean ± SD CTT was significantly greater for young horses (47.50 ± 4.52 mm) than for horses in the old (28.06 ± 5.72 mm) and PPID (21.5 ± 3.37 mm) groups. Old horses had significantly higher CTT values than did horses with PPID. The STT values were within the reference range for all groups and did not differ significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Corneal sensitivity decreased with both age and PPID. Because decreased corneal sensitivity is associated with impaired wound healing, increasing age and PPID may increase the risk for nonhealing or recurrent corneal ulcers in horses.

α-Melanocyte--stimulating hormone and adrenocorticotropin concentrations in response to thyrotropin-releasing hormone and comparison with adrenocorticotropin concentration after domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction.

OBJECTIVE: To compare endogenous ACTH and α-melanocyte-stimulating hormone (α-MSH) concentrations after administration of thyrotropin-releasing hormone (TRH) and to compare ACTH concentrations after TRH administration with those following domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction (PPID). DESIGN: Prospective case series. ANIMALS: 69 clinically normal horses and 47 horses with or suspected to have PPID. PROCEDURES: ACTH concentrations were measured during 108 TRH stimulation tests in 88 horses, and α-MSH concentrations were measured during 56 TRH stimulation tests in 50 horses. In 28 of these horses, ACTH concentrations after domperidone administration were measured and test results were compared. The pituitary gland was histologically examined in all horses that were euthanatized. RESULTS: ACTH and α-MSH concentrations increased in all horses after TRH administration, with a greater and more prolonged increase in horses with PPID. Percentage increase was significantly greater for α-MSH concentration than for ACTH concentration. The change in ACTH concentration after domperidone administration was less consistent in differentiating clinically normal horses from those with PPID than was the response to TRH. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ACTH concentration in response to TRH administration was useful for the diagnosis of PPID in horses and appeared more accurate than response to domperidone administration. Use of an α-MSH concentration ≥ 30 or 50 pmol/L did not appear superior to use of an ACTH concentration ≥ 36 pg/mL for the diagnosis of PPID, either before or 30 minutes after TRH administration.

Meningitis, cranial neuritis, and radiculoneuritis associated with Borrelia burgdorferi infection in a horse.

CASE DESCRIPTION: A 12-year-old Thoroughbred was examined because of signs of depression, neck stiffness, and poor performance. CLINICAL FINDINGS: Physical examination revealed that the horse was dull, appeared depressed, was reluctant to raise its neck and head above a horizontal plane, and had a temperature of 38.5°C (101.3°F). No radiographic or scintigraphic abnormalities of the neck were found; however, high plasma fibrinogen concentration and relative lymphopenia were identified and the horse was seropositive for antibodies against Borrelia burgdorferi. Analysis of CSF revealed neutrophilic inflammation, and results of a PCR assay of CSF for B burgdorferi DNA were positive. Immunologic testing revealed severe B-cell lymphopenia and a low serum IgM concentration consistent with common variable immunodeficiency. TREATMENT AND OUTCOME: The horse responded well to do×ycycline treatment (10 mg/kg [4.5 mg/lb], PO, q 12 h for 60 days) and returned to normal exercise. However, 60 days after treatment was discontinued, the horse again developed a stiff neck and rapidly progressive neurologic deficits, including severe ataxia and vestibular deficits. The horse's condition deteriorated rapidly despite IV oxytetracycline treatment, and the horse was euthanatized. Postmortem examination revealed leptomeningitis, lymphohistiocytic leptomeningeal vasculitis, cranial neuritis, and peripheral radiculoneuritis with Wallerian degeneration; findings were consistent with a diagnosis of neuroborreliosis. CLINICAL RELEVANCE: Nervous system infection with B burgdorferi should be considered in horses with evidence of meningitis and high or equivocal serum anti-B burgdorferi antibody titers. Evaluation of immune function is recommended in adult horses evaluated because of primary bacterial meningitis.

Evaluation of plasma ACTH, alpha-melanocyte-stimulating hormone, and insulin concentrations during various photoperiods in clinically normal horses and ponies and those with pituitary pars intermedia dysfunction.

OBJECTIVE: To measure plasma ACTH, alpha-melanocyte-stimulating hormone (aloha-MSH), and insulin concentrations during various photoperiods between February and October in horses and ponies with and without pituitary pars intermedia dysfunction (PPID). DESIGN: Cohort study. ANIMALS: 13 clinically normal (control) ponies, 14 clinically normal (control) horses, 7 ponies with PPID, and 8 horses with PPID. PROCEDURES: Blood samples were collected from February through October during 8 photoperiods: 1, February 13 through March 2; 2, April 4 through 6; 3, June 19 through 22; 4, August 6 through 7; 5, August 14 through 17; 6, September 4 through 6; 7, September 26 through 28; and 8, October 16 through 18. Plasma ACTH, alpha-MSH, and insulin concentrations at each photoperiod were compared among groups. RESULTS: Log ACTH concentration was increased during photoperiod 4 through 8, compared with photoperiod 1 through 3, in all groups. In photoperiod 3 through 7, log ACTH concentrations were higher in horses and ponies with PPID, compared with values for control horses and ponies. alpha-Melanocyte-stimulating hormone (log and raw value) concentration was higher in photoperiod 2 through 8, compared with photoperiod 1, in control horses and ponies. In horses and ponies with PPID, log alpha-MSH concentration was higher in photoperiod 3 through 8, and alpha-MSH concentration was higher in photoperiod 4 through 8, compared with photoperiod 1. In control horses and ponies, plasma insulin concentration was lower in photoperiod 3 than in photoperiod 1. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma alpha-MSH and ACTH concentrations increased as daylight decreased from summer solstice (maximum daylight hours) to 12 hours of daylight.

A multicenter case-control study of risk factors for equine protozoal myeloencephalitis.

OBJECTIVE: To identify risk factors for equine protozoal myeloencephalitis (EPM) among horses examined at 11 equine referral hospitals. DESIGN: Case-control study. ANIMALS: 183 horses with EPM, 297 horses with neurologic disease other than EPM (neurologic controls), and 168 horses with non-neurologic diseases (non-neurologic controls) examined at 11 equine referral hospitals in the United States. PROCEDURES: A study data form was completed for all horses. Data were compared between the case group and each of the control groups by means of bivariate and multivariate polytomous logistic regression. RESULTS: Relative to neurologic control horses, case horses were more likely to be > or = 2 years old and to have a history of cats residing on the premises. Relative to non-neurologic control horses, case horses were more likely to be used for racing or Western performance. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that cats may play a role in the natural epidemiology of EPM, that the disease is less common among horses < 2 years of age relative to other neurologic diseases, and that horses used for particular types of competition may have an increased risk of developing EPM.

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.

Suspected panosteitis in a camel.

CASE DESCRIPTION: A 6-month-old male Bactrian camel was examined because of a 3-week history of lameness of the left hind limb. CLINICAL FINDINGS: Lameness was initially detected in the left hind limb but resolved and was detected in the right hind limb during treatment. Lameness increased during periods of rapid growth. Radiography revealed multiple small opacities of the medullary cavity of several long bones throughout treatment. Core bone biopsies of lesions in the tibiae revealed lamellar bone with areas of loose connective tissue, osteoblasts in the medullary cavity, and periosteal new bone formation, all which were consistent with panosteitis. TREATMENT AND OUTCOME: Palliative treatment was attempted with epidural and transdermal administration of analgesics. Flunixin meglumine was administered PO, which coincided with an abrupt increase in serum creatinine concentration. Performance of multiple diagnostic bone biopsies led to remission of clinical signs of pain. CLINICAL RELEVANCE: Panosteitis should be a differential diagnosis for shifting limb lameness in young camels. Bone biopsies can be useful for diagnosis of panosteitis and possible relief of pain associated with the disease. Bactrian camels may be susceptible to the renal toxicity of flunixin meglumine, especially when dehydrated.

Effects of electrostimulated acupuncture on ground reaction forces and pain scores in dogs with chronic elbow joint arthritis.

OBJECTIVE: To determine whether use of electrostimuluated acupuncture (ESA) would result in significant improvements in ground reaction forces and lameness scores in dogs with chronic elbow joint osteoarthritis secondary to elbow joint dysplasia. DESIGN: Randomized, controlled, crossover clinical trial. ANIMALS: 9 dogs with chronic forelimb lameness and radiographic evidence of elbow joint osteoarthritis. PROCEDURES: All dogs had a 3-week control acclimation period during which gait analysis was performed weekly. Dogs then received ESA once weekly for 3 weeks followed by a sham treatment once weekly for 3 weeks or received the sham treatment followed by ESA. Gait analysis was repeated prior to each treatment, and owners were asked to provide pain scores by use of a visual analog scale method. RESULTS: Treatment (control, acupuncture, or sham) did not have a significant effect on ground reaction forces for any limb. Owners of 8 of the 9 dogs were able to correctly guess the time period when ESA was delivered. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ESA did not have any significant effects on severity of lameness, as determined by measurement of ground reaction forces, or severity of pain, as determined by visual analog scale pain scores, in dogs with chronic elbow joint osteoarthritis secondary to elbow joint dysplasia.

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 observed in horses likely differs. We proposed that TRH directly stimulates the PI in normal and PPID-affected horses to release proopiomelanocortin (POMC) derived peptides. Using alpha-melanocyte stimulating hormone (alpha-MSH) as a marker of a PI response and ACTH as a marker of a PD response, we were able to demonstrate a marked increase in plasma concentration of alpha-MSH and a modest, but significant increase in ACTH after TRH treatment in normal horses. The ability of TRH to directly stimulate release of POMC peptides was confirmed using PI and PD tissue explants. The presence of TRH receptor mRNA in PI tissue from both normal and PPID horses was confirmed using reverse transcriptase polymerase chain reaction. We conclude that TRH triggers the release of POMC-derived peptides from the PI through the direct stimulation of TRH receptors normally expressed on melanotropes. The increase in plasma cortisol following TRH in horses with PPID is likely attributable to the release of ACTH from the hyperplastic PI.

Evaluation of risk factors for development of catheter-associated jugular thrombophlebitis in horses: 50 cases (1993-1998).

OBJECTIVE: To evaluate risk factors associated with development of catheter-associated jugular thrombophlebitis in hospitalized horses. DESIGN: Retrospective case-control study. ANIMALS: 50 horses with thrombophlebitis and 100 control horses. PROCEDURE: Medical records from 1993 through 1998 were searched for horses with thrombophlebitis. Horses that were hospitalized for at least 5 days, had an i.v. catheter placed in a jugular vein (other than for solely anesthetic purposes), and had no evidence of thrombophlebitis during admission or hospitalization were chosen as controls. Signalment, history, clinicopathologic findings, primary illness, and treatment were obtained from the medical records. Data were analyzed by use of logistic regression to perform univariate and multivariate analyses. RESULTS: For a horse with endotoxemia, the odds of developing thrombophlebitis were 18 times those for a similar horse without endotoxemia. For a horse with salmonellosis, the odds of developing thrombophlebitis were 68 times those for a similar horse without salmonellosis. For a horse with hypoproteinemia, the odds of developing thrombophlebitis were almost 5 times those for a similar horse without hypoproteinemia. For a horse in the medicine section, the odds of developing thrombophlebitis were 16 times those for a similar horse in the surgery section. For a horse with large intestinal dise, the odds of developing thrombophlebitis were 4 times those for a similar horse without large intestinal disease. For a horse receiving antidiarrheal or antiulcerative medications, the odds of developing thrombophlebitis were 31 times those for a similar horse not receiving these medications. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that patient factors, including large intestinal disease, hypoproteinemia, salmonellosis, and endotoxemia, were associated with development of catheter-associated thrombophlebitis in horses.

Common variable immunodeficiency in three horses with presumptive bacterial meningitis.

Three adult horses were evaluated for signs of musculoskeletal pain, dullness, ataxia, and seizures. A diagnosis of bacterial meningitis was made on the basis of results of CSF analysis. Because primary bacterial meningitis is so rare in adult horses without any history of generalized sepsis or trauma, immune function testing was pursued. Flow cytometric phenotyping of peripheral blood lymphocytes was performed, and proliferation of peripheral blood lymphocytes in response to concanavalin A, phytohemagglutinin, pokeweed mitogen, and lipopolysaccharide was determined. Serum IgA, IgM, and IgG concentrations were measured by means of radial immunodiffusion, and serum concentrations of IgG isotypes were assessed with a capture antibody ELISA. Serum tetanus antibody concentrations were measured before and 1 month after tetanus toxoid administration. Phagocytosis and oxidative burst activity of isolated peripheral blood phagocytes were evaluated by means of simultaneous flow cytometric analysis. Persistent B-cell lymphopenia, hypogammaglobulinemia, and abnormal in vitro responses to mitogens were detected in all 3 horses, and a diagnosis of common variable immunodeficiency was made.

Variation in plasma adrenocorticotropic hormone concentration and dexamethasone suppression test results with season, age, and sex in healthy ponies and horses.

The purpose of this study was to evaluate the variation in plasma adrenocorticotropic hormone (ACTH) concentration and dexamethasone suppression test (DST) results with season, age, and sex in healthy, pony mares (n=15) and pony stallions (n=14) living under semiferal conditions and horse mares (n=10) living at pasture. Plasma ACTH concentrations were measured in September 2002, and in January, May, and September 2003. DSTs were performed in January and September 2003. Plasma ACTH concentrations in September 2002 and September 2003 were similar and were significantly greater than in January and May (P < .001). Plasma ACTH concentration was within the reference range for 38 (97%) of 39 subjects in January, for 39 (100%) of 39 subjects in May, for 2 (5%) of 39 subjects in September 2002, and for 3 (8%) of 39 subjects in September 2003. DST results were within the reference range in all subjects in January and were within the reference range for 29 (74%) of 39 subjects in September 2003. Plasma cortisol concentration at the end of the DST was significantly greater in September than in January (P = .002). Age was positively correlated with plasma ACTH and plasma cortisol concentration at the beginning and end of the DST Within the same season, plasma ACTH concentration in pony mares, pony stallions, and horse mares was not significantly different (P > .05). Seasonal changes in plasma ACTH concentration and DST results should be considered when interpreting endocrine test results.

Correlation between plasma alpha-melanocyte-stimulating hormone concentration and body mass index in healthy horses.

OBJECTIVE: To evaluate the correlation between plasma alpha-melanocyte-stimulating hormone (alpha-MSH) concentration and body mass index (BMI) in healthy horses. ANIMALS: 82 healthy horses. PROCEDURE: Plasma alpha-MSH concentration was determined by radioimmunoassay. At the time blood samples were collected, body condition scores (BCS) were determined and measurements of girth circumference, body length, and height were obtained. Weight was estimated by use of the following formula: estimated weight (kg) = [girth (cm)2 x length (cm)]/11,877. Body mass index was calculated as estimated weight (kg)/height (m)2. RESULTS: A correlation was found between BMI and BCS (rs = 0.60 [95% confidence interval (CI), 0.44 to 0.731). A weak correlation was found between plasma alpha-MSH concentration and BMI (rs = 0.25 [95% CI, 0.03 to 0.45]) and BCS (rs = 0.26 [95% CI, 0.04 to 0.46]). A correlation was found between plasma alpha-MSH concentration and BMI in horses > or = 10 years old (rs = 0.49 [95% CI, 0.20 to 0.69]) but not in horses < 10 years old (rs = -0.04). Horses in the upper quartile of BMI had significantly greater plasma alpha-MSH concentration (median, 9.1 pmol/L; range, 2.0 to 95.3 pmol/L) than horses in the lowest quartile of BMI (median, 70 pmol/L; range, 3.6 to 15.7 pmol/L). CONCLUSIONS AND CLINICAL RELEVANCE: A correlation exists between plasma alpha-MSH concentration and BMI in horses. Further study is required to determine whether melanocortin receptor defects underlie this correlation or, alternately, whether plasma alpha-MSH concentration is simply a correlate of adiposity.

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.

Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing's disease).

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; range, 4.2-173) were significantly lower (P < .01) than those in horses treated with cyproheptadine (n = 7; median = 141.0 pg/ml: range, 10-1,230). Among horses treated with pergolide, there was a correlation between ACTH concentration after treatment and the duration of treatment (P < .001) and pergolide dose (P = .04). Significantly (P = .02) more owners of horses treated with pergolide (85%, 17/20) reported an improvement in clinical signs compared to owners of horses treated with cyproheptadine (28%, 2/7).