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Keywords:

  • horse;
  • geriatric;
  • epidemiology;
  • equine Cushing's syndrome;
  • endocrine

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References

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.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References

Equine pituitary pars intermedia dysfunction (PPID or equine Cushing's syndrome) is a disorder of aged horses resulting from a loss of dopaminergic inhibition of the pars intermedia of the pituitary [1]. A proposed pathophysiological mechanism leading to PPID is oxidative stress and neurodegeneration in the dopaminergic neurones of the hypothalamus causing a decrease in dopamine production [2–5]. The result is a loss of negative control of pars intermedia endocrine function and overproduction of proopiomelanocortin (POMC) derived peptides produced by the pars intermedia melonotrope cells including adrenocorticotropic hormone (ACTH), alpha melanocyte stimulating hormone (α-MSH), beta endorphin (β-endorphin) and corticotrophin-like intermediate peptide (CLIP) [2,4–6]. McFarlane [3] suggested that the neurodegenerative process leading to PPID is associated with ageing, a finding supported by an increasing occurrence in older horses. For example, studies on horses with PPID have reported a mean age of 19 [7] and 27 [8] years.

Equine PPID manifests in a variety of ways. The most commonly reported signs are excessive hair coat length and/or delayed coat shedding (hirsutism), signs of depression, weight loss and increased muscle catabolism resulting in a wasted epaxial musculature (or ‘top line’) and a pendulous abdomen (or ‘pot belly’), redistribution of body fat resulting in bulging supraorbital fat, polyuria and polydipsia (PU/PD), chronic infections and laminitis [9,10]. Unequivocal hirsutism has been considered pathognomonic for PPID [11] and the demonstration of either hirsutism or hirsutism and one or more other clinical signs of PPID has been used as a means for diagnosis of PPID [12–14]. However, hirsutism is more specific than sensitive [15] and further diagnostic testing is warranted. Basal endocrine tests are popular due to their simplicity and are ideal for epidemiological studies where large numbers of horses are sampled. Basal plasma α-MSH and ACTH concentrations have been shown to be both sensitive and specific for the diagnosis of PPID when seasonally adjusted reference ranges are used [16]. However, basal plasma α-MSH had a lower sensitivity (59%) than basal plasma ACTH (80%) in winter, spring and summer [16] and basal plasma α-MSH is not commercially available as a diagnostic test in horses. Therefore, in this study, the prevalence was defined on the basis of elevated basal plasma ACTH concentrations.

The prevalence of PPID in the aged equine population is not well documented and available reports appear to be complicated by the criteria used for diagnosis and population selection. In one population of 165 horses aged 20 years or older, there was a prevalence of veterinarian diagnosed PPID of 8%, while 30% of the same group had changes in hair coat compatible with PPID [17]. The authors do not report the selection criteria for their population and it is therefore difficult to determine how representative it may be of the general horse population. A second study by the same group investigating horses ≥20 years of age, admitted to a veterinary teaching hospital, revealed a prevalence of PPID of 10% based on clinical signs and increased ACTH concentration [8]. A small pilot study in the UK examined 23 apparently healthy horses with a median age of 26.5 years and found 39% with PPID [18]. A separate study in the UK suggested that the prevalence of PPID to be as low as <1% [19], but this study was not restricted by age of the horse and relied on owner-reported diagnosis.

The aim of this study was to determine the prevalence, risk factors and clinical signs predictive for PPID using seasonally-adjusted cut-off values for basal plasma ACTH concentrations in a population of horses aged 15 years or greater in south east Queensland, Australia (SE QLD).

Materials and methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References

Ethical approval was obtained by the University of Queensland Ethical Review Committee and Animal Ethics Committee.

Study 1 (survey data) consisted of a questionnaire designed to obtain data on horses aged 15 years or greater in SE QLD. Details of the selection criteria have been provided elsewhere [20]. Data were collected on horse details, history, owner-reported clinical signs, management practices and owners' welfare concerns of aged horses. A history of owner-reported hirsutism was determined on the basis of their responses on the questionnaire concerning hair coat changes detected in their horse and was considered to be present if the owner had indicated that their horse was showing signs of a long hair coat and/or delayed shedding and/or failure to shed.

Study 2 (clinical data) consisted of a sub-sample of the population in Study 1 and was restricted to aged horses owned by members of Equestrian Queensland (EQ) who resided within defined geographical regions of SE QLD. These regions were Brisbane City, Gold Coast and hinterlands, Sunshine Coast and hinterlands, Ipswich and Lockyer Valley, Toowoomba and surrounds and Warwick and surrounds. In addition, they needed to have provided their name and address to indicate willingness to participate further in the study. These owners were contacted and a date for the clinical examination of their aged horse or horses was set. During each visit all aged horses owned by the member underwent a complete clinical examination and blood sample collection by a veterinary surgeon.

Blood samples were analysed for routine haematology (Beckman Coulter AcT Diff Anaylser)a and selected biochemistry analysis (Olympus AU400 Automated Chemistry Analyser)b, serum insulin (RIA, DSL), plasma ACTH (Immulite 1000 assay)c and plasma α-MSH (RIA, Euro diagnostica, Euria alpha-MSH RIA Kit)d concentrations. Laboratory findings were compared with owner-reported clinical signs and clinical examination findings.

For the purposes of this study, a horse was considered positive for PPID on laboratory findings if there were increases in basal plasma ACTH concentrations above seasonally adjusted reference ranges derived using the Youden index for the population and region under study [16,21]. These values were 77.4 pg/ml for autumn and 29.7 pg/ml for all other seasons [16].

Univariable analysis was performed to investigate associations between aged horses with PPID based on elevation of basal plasma ACTH concentrations compared with aged horses without elevation. Variables analysed included horse case details (age, pony vs. horse, gender), owner-reported clinical signs, haematological and biochemical variables and veterinary clinical examination findings. Pearson's χ2 P values were calculated and where group numbers for categorical variables were less than 5, Fisher's exact P values were used. Significance was set at P≤0.05. Odds ratios (OR) were then calculated with 95% confidence intervals (CI).

A Mann-Whitney or student t test was used to compare advanced PPID horses (those with hirsutism plus 3 or more clinical signs of PPID) and those with a positive test and no hirsutism or hirsutism and 0, 1 or 2 clinical signs of PPID (PPID). Significant results were presented as median and interquartile range (IQR). Univariable linear regression analysis was performed to assess the association of absolute lymphocyte count to the age of the horse, ACTH concentration and total number of historical and clinical signs.

Multivariable binary logistic regression analysis was performed in a backward stepwise approach, based on significant univariable findings, to assess factors associated with a binary outcome of PPID (positive, negative). If removal of a nonsignificant factor resulted in a coefficient changing by more than 10%, the factor was considered a confounder and retained in the model. Interaction terms were introduced and removed in a similar fashion. The Hosmer-Lemeshaw goodness of fit test was used to assess significance and goodness of fit. Receiver operating characteristics (ROC) curve plots were used to assess the predictive power of the model.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References

Study 1 (survey data): Completed questionnaires were received from 536 owners of 2873 horses. Of the total number of horses owned, 37.9% (1089/2873) were aged 15 years or greater. The 536 owners returned a total of 974 complete questionnaires on their aged horses, representing 89.4% (974/1089) of horses aged 15 years or over.

The prevalence of owner-reported hirsutism was 16.7% (95% CI 14.4–19.1) (163/974) [22]. Owners indicated they had observed many of the clinical signs commonly associated with PPID. The 3 signs most frequently reported by owners that may be associated with PPID were weight loss (16.8%), signs of depression (7.6%) and laminitis (4.8%) [16,22].

Study 2 (clinical data): A veterinary clinical examination was performed on 35.6% (347/974) of the aged horses from Study 1. Clinical data was missing for 7 horses and blood samples missing from a further horse; data from the remaining 339 are presented in this paper. Of these, 14 horses did not have ACTH measured; therefore only 325 aged horses had both values available.

In this subgroup, the prevalence of owner-reported hirsutism was 14.2% (95% CI 10.4–17.9) (48/339). Seventy-five horses (22%) were tested in the autumn, while the remaining 264 (78%) horses were tested outside the autumn period. The prevalence of PPID in aged horses was 21.2% (69/325) (95% CI 16.9–26.1) based on increases of basal plasma ACTH concentration above the seasonally adjusted cut-off values. Elevated plasma α-MSH above the seasonally adjusted reference ranges was found in 11.7% of aged horses (38/325) and elevations of either basal plasma α-MSH or ACTH concentrations were found in 22.2% (72/325) (95% CI 18.0–27.2) of aged horses.

Aged horses diagnosed with PPID using basal plasma ACTH concentrations (n = 69) were significantly older (median 24 years, IQR 20–27 years) than aged horses with a negative test (n = 256) (median 18.8 years, IQR 16–21.5 years) (P<0.001). There was no significant difference in median age of ponies compared with horses (P = 0.3). Age had a moderate significant linear correlation (r2= 0.4, P<0.001) with loge ACTH.

Univariable analysis

Aged horses diagnosed with PPID (n = 69) were compared with aged horses without elevations of basal plasma ACTH concentrations (n = 256) using univariable analysis. There was no association of gender or pony vs. horse with a positive diagnosis of PPID. However, age was found to be associated with a positive test with an increased risk for every year of age from 15 years. There was an association between a positive diagnosis of PPID and many historical factors, veterinary clinical examination findings and haematological and biochemical results consistent with the diagnosis (Table 1). The proportion of aged horses with or without a positive diagnosis of PPID with each historical factor or sign is also shown in Table 1.

Table 1.  Univariable analysis for risk factors and clinical signs predictive for a positive diagnosis of pituitary pars intermedia dysfunction
Risk factorORCIPProportion exposed (of 69 cases)Proportion unexposed (256 controls)
  1. OR = odds ratio, CI = 95% confidence interval, P = probability. *P≤0.05

Case details      
 Age1.201.13–1.28<0.001*N/AN/A
 Gender (Ref. female)0.980.55–1.770.9362%63%
 Pony vs. horse (Ref. Pony)1.580.77–3.150.1623%16%
Historical factors      
 Owner-reported history of hirsutism10.244.83–21.97<0.001*41%6%
 Depression/lethargy2.110.83–5.050.0714%7%
 Increased appetite3.830.50–29.10.084%1%
 Polydipsia3.880.70–21.29<0.05 (not significant)6%2%
 Polyuria3.900.87–17.5<0.03 (not significant)7%2%
 Laminitis4.651.50–14.4<0.001*13%3%
Clinical examination findings      
 Hirsutism6.242.96–13.10= 0.001*33%7%
 Wasted topline2.441.36–4.36<0.01*48%27%
 Pot belly2.271.15–4.39<0.01*29%15%
 Bulging supraorbital fat2.961.21–6.98<0.01*17%7%
 Divergent rings4.011.15–13.890.01*10%3%
 Separation of the white line1.700.83–3.460.123%15%
 Body mass index0.990.98–1.000.2N/A 
Haematological and biochemical results      
 Packed cell volume0.140.001–18.90.4N/A 
 White cell count1.060.92–1.210.4N/A 
 Neutrophils1.040.86–1.250.7N/A 
 Lymphocytes1.040.76–1.430.8N/A 
 Fibrinogen1.231.00–1.520.048*N/A 
 Aspartate transaminase1.001.00–1.000.6N/A 
 Creatine phosphokinase1.001.00–1.000.8N/A 
 Gamma glutamyltransferase1.041.00–1.080.048*N/A 
 Total protein1.051.00–1.100.04*N/A 
 Albumin1.071.00–1.160.2N/A 
 Globulins1.031.00–1.070.3N/A 
 Bilirubin1.001.00–1.000.6N/A 
 Basal hyperinsulinaemia (≥20 µiu/ml)2.671.37–5.12= 0.001*32%3%

All haematological and biochemical variables were assessed as continuous variables. Higher fibrinogen, gamma glutamyltransferase, total protein and insulin were associated with aged horses diagnosed with PPID (P<0.05) (Table 1). However, of these, only serum insulin had a confidence interval which did not include 1. Furthermore, when the values for PPID positive and negative aged horses are tabulated it can be seen that the median and IQRs for these variables lie within the reference ranges for the laboratory, except insulin where 32% of aged horses with a diagnosis of PPID were hyperinsulinaemic (Table 2). Within the PPID positive horses, advanced cases (those with hirsutism plus 3 or more clinical signs, n = 20) were not different from the rest of the PPID positive horses (n = 49) for fibrinogen concentration (P = 1.0), gamma glutamyltransferase (P = 0.1), total protein (P = 0.9), total white cell count (P = 0.4) and neutrophils (P = 0.6). However, aged horses with advanced PPID were significantly older (27, IQR 22.5–30 years vs. 23, IQR 20–27 years) (P<0.02). Aged horses with advanced PPID also had lower lymphocyte counts (1.7, IQR 1.3–2.4) than those horses with PPID (2.3, IQR 1.9–2.8) (P<0.01), but were not lower than those horses that were PPID negative (P = 0.12) (Fig 1). Age, ACTH concentration and number of clinical signs were not significantly associated with total lymphocyte count.

Table 2.  Haematological and biochemical variables for horses diagnoses with pituitary pars intermedia dysfunction (PPID) (n = 69) compared with horses without elevations in either plasma α-MSH or ACTH (n = 256)
VariableMedian (IQR) PPID positiveMedian (IQR) PPID negativeReference range
  1. IQR = interquartile range.

Packed cell volume (l/l)38 (34–42)39 (36–43)35–43
Haemoglobin (g/dl)13.2 (12.0–14.7)13.6 (12.4–14.7)12.5–15.5
Red cell count × 1012/l7.4 (6.7–8.2)7.78 (7.2–8.5)7.02–9.02
Mean corpuscular haemoglobin concentration (g/dl)35 (33–36)35 (33–36)32–37
Mean corpuscular haemoglobin (pg)18 (17–19)17.5 (17–19)16–19
Mean corpuscular volume (fl)52 (49–54)51 (48–53)45–53
Platelet count147.5 (103–201)143 (105–181)100–350
White cell count × 109/l7.7 (6.8–9.1)7.6 (6.5–8.8)6.4–11.0
Neutrophil count × 109/l4.6 (3.8–5.4)4.5 (3.7–5.3)2.5–7.0
Lymphocyte count × 109/l2.2 (1.6–2.6)2.0 (1.6–2.7)1.6–5.4
Monocyte count × 109/l0.4 (0.3–0.5)0.4 (0.2–0.6)<0.8
Eosinopil count × 109/l0.4 (0.2–0.6)0.3 (0.1–0.6)<0.9
Basophil count × 109/l0 (0–0.1)0 (0–0.1)<0.4
Fibrinogen (g/l)3 (3–4)3 (2–4)2–4
Total protein (g/l)71 (67–75)69 (66–72)57–79
Albumin (g/l)35 (32–36)34 (32–35)23–39
Globulins (g/l)37 (32–40)35 (32–39)26–40
Aspartate transaminase (u/l)256 (228–325)259 (225–296)<350
Creatine kinase (u/l)229 (170–318)236 (173–308)<350
Gamma glutamyltransferase (u/l)14 (12–19)14 (11–16)7–41
Creatinine (µmol/l)96 (84–110)102 (88–120)20–168
Total bilirubin (mmol/l)19.5 (16.1–23.7)22 (16.6–27.3)0.5–34
Insulin (µiu/ml)13.3 (8.3–24.7)8.2 (4.0–14.3)≤20
image

Figure 1. Box plot showing lymphocyte count (×109/l) for aged horses ≥15 years old with advanced pituitary pars intermedia dysfunction (advanced PPID, n = 20) compared with less advanced (PPID, n = 49) and age-matched controls (n = 256).

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Aged horses with PPID were more likely to suffer from laminitis than aged horses without PPID (Table 1). Overall, hyperinsulinaemia was associated with a history of laminitis in all 337 aged horses (OR 10.4, 95% CI 3.7–31.7, P<0.001). Of the 21/337 (6.2%) aged horses with a history of laminitis 14 (66%) were hyperinsulinaemic. Of the 9/69 (13%) aged horses in the PPID positive group with a history of laminitis, 6 aged horses (66%) were hyperinsulinaemic and laminitis was associated with hyperinsulinaemia (OR 5.5, 95% CI 1.0–37.0, P = 0.016). Of the 8/255 (3.1%) aged horses in the PPID negative group with a history of laminitis, 4 aged horses (50%) were hyperinsulinaemic and hyperinsulinaemia was associated with laminitis (OR 6.3, 95% CI 1.1–34.9, P = 0.005).

Multivariable analysis

Multivariable binary logistic regression modelling found the best model to predict a positive diagnosis of PPID to include age as a continuous variable and a history of (owner-reported) hirsutism. No other variables from the univariable analysis were found to be significant, confounders or improved the model. The OR for age as a continuous variable was 1.18 (95% CI 1.11–1.25) (P<0.001) and the OR for an owner-reported history of hirsutism was 7.80 (95% CI 3.67–16.57) (P<0.001). The model showed no evidence of a lack of fit using the Hosmer-Lemshaw goodness of fit test (P>0.05). The ROC curve used for assessing the model showed a good predictability of 0.80 (Fig 2).

image

Figure 2. Receiver operating characteristics (ROC) curve plots used to assess the predictive power of the final logistic regression model showed an area under the curve (AUC) = 0.92 indicating a good result.

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Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References

The current study has shown the prevalence of PPID in horses aged 15 years and older to be 21% based on the criteria of basal plasma ACTH concentrations being elevated above seasonally adjusted reference ranges [16]. This prevalence corresponds with the prevalence of hirsutism (22%) observed in a comparable study of aged horses aged 15 years and older from the UK [23], although it is greater than the hirsutism reported in the current study by owners (14%). However, in either case, the prevalence is high enough to warrant a high suspicion of PPID in horses aged 15 years and older demonstrating any of the clinical signs associated with PPID. This high prevalence and the increased prevalence with increasing age shown in the multivariable logistic regression model, support that PPID is a degenerative disease associated with ageing [3] rather than a spontaneously occurring disease. The high prevalence may also be a reflection of a relatively low mortality in a disease from which horses do not recover.

This study represents the first large epidemiological study of PPID in aged horses in a population unbiased by presentation to or records obtained from veterinary practices. Most studies have been based on referral hospital populations or populations that relied on veterinary clinic databases of owners [8,19]. This study population was derived from horses owned by members of an equestrian association. Although it is not representative of the entire population of horse owners, this type of sample population may more closely represent the spectrum of PPID amongst aged horses, rather those with clear clinical evidence of advanced disease as has been the focus of veterinary hospital or research herd-based studies.

It has been suggested that many horse owners may defer seeking veterinary advice for their horses unless the condition is ‘serious’[24]. Many of the signs of PPID are nonspecific such as weight loss and depression. Others including muscle wasting, pot belly and hirsutism have erroneously been considered normal signs of ageing in horses [25]. Therefore, owners recognising these signs may not regard them as important enough to seek veterinary advice. In this group of aged horses, owners reported PPID or synonym in only 1.6% (16/974) of horses [22]. The under-recognition of PPID is further supported by reports of low prevalence of PPID in population-based studies [19] compared with veterinary [18] or histopathological studies [26]. Similarly, Brosnahan and Paradis [17] found a much lower prevalence of a veterinary diagnosis of PPID (8%) than clinical signs of PPID (30%) in a small population-based study. This study attempted to overcome this discrepancy in the study group by contacting horse owners via an equestrian organisation for survey data (Study 1) and by subsequently performing veterinary clinical examinations and laboratory testing on a geographically determined subset of these aged horses (Study 2).

Signs commonly reported to be associated with PPID are long hair coat and/or failure to shed hair coat appropriately (hirsutism), recurrent laminitis, depression or lethargy, chronic hoof abnormalities (divergent rings, separation of the white line or ‘seedy toe’), polyuria/polydipsia and redistribution of body mass (pot belly, supraorbital fat and wasting of the epaxial muscles) [1,27]. All these clinical or historical signs were significant predictors for a diagnosis of PPID on the univariable model. However, all these clinical and historical signs are related by the underlying disease. It is for this reason that almost all of these clinical signs failed to be retained in the multivariable model, with only owner-reported hirsutism remaining as the most predictive of a diagnosis of PPID.

Using a multivariable model, only age and a history of hirsutism were significant predictors of a diagnosis of PPID. The retention of owner-reported hirsutism supports the contention that owners can detect hirsutism better than a veterinary clinical examination, as some horses display hirsutism variably throughout the year [16]. An owner has the benefit of comparing coat shedding patterns and coat length from an historical and seasonal perspective. A variety of risk or associated factors have been proposed to be associated with a clinical or laboratory diagnosis of PPID, most notably the pony breed [1], but also previous obesity or equine metabolic syndrome. The results of this study do not support any direct effect of pony breed or body mass index as risk factors for PPID. However, when age, breed and sex were analysed in a multivariable model against owner-reported clinical signs of disease, hirsutism was more likely to be reported in ponies than other breeds [22]. Ponies may express hirsutism more obviously than horses prompting owners to seek veterinary advice, which may explain the belief that ponies are more commonly affected by PPID.

Previous studies have reported various haematological and biochemical difference in blood tests from horses with PPID [1,28]. In this study the only differences that were detected involved variables where the median and IQR all fell within the reference range. This was examined further by comparing advanced and less advanced PPID horses with no differences detected except for a lower lymphocyte count in the advanced cases. The median relative lymphopenia was again still within reference ranges and advanced cases were not different from the PPID negative horses. Advanced cases were significantly older and lymphopenia has been found in previous studies in older groups of aged horses where 13 and 17% horses aged 30 years and older and 20 years and older, respectively, showed lymphocyte counts below the laboratory reference ranges [29,30]. Lymphopenia has been reported to be associated with ageing and immunosenescence [31]. Lower lymphocyte counts can also be caused by hyperadrenocorticism [28]. However, on analysis of factors associated with lymphopenia in the current study, neither increased age (above 15 years) nor indicators of the degree of PPID (ACTH concentration and number of clinical signs) were significantly associated. Therefore, from the results of this study, there were no haematological or biochemical variables supportive of a diagnosis of PPID. Aged horses with PPID did not develop a ‘stress leucogram’[27]. Any haematological or biochemical changes in aged horses with PPID should be interpreted as indicators of inflammation or disease in addition to the underlying PPID and not as an expected concurrent finding.

Plasma insulin concentration was elevated above the reference range for 32% aged horses with PPID indicative of a degree of insulin resistance in affected horses [1]. Hyperinsulinaemia has been associated with a reduced prognosis in horses with PPID [32] usually attributed to the increased risk of laminitis associated with insulin resistance [33]. While horses with PPID were more likely to be hyperinsulinaemic and the presence of hyperinsulinaemia associated with an increase risk of laminitis, these associations were similar for all aged horses in this study and not unique to horses with a diagnosis of PPID. The findings of this study support an association between insulin and laminitis, but do not provide any further information about potential causes of insulin resistance in the aged horses studied.

A history of laminitis was only reported by owners in 5% of aged horses examined, although 10% had divergent rings detected on clinical examination. This is a lower proportion of horses affected by laminitis than in reports based on clinical case series of laminitis [1] and may reflect management practices in Queensland where owners may be less likely to keep aged horses with chronic or recurrent laminitis. It may also be reflective of owner selection affecting previous case series, where aged horses with signs of PPID are not considered to have a problem serious enough to involve their veterinary surgeon until they develop laminitis [24].

In conclusion, PPID was prevalent (21%) in horses 15 years and older, with an increasing prevalence with each year of age. A history of hirsutism as detected by the owner on the basis of delayed shedding, failure to shed or the presence of a long hair coat was the only clinical or historical sign associated with a laboratory diagnosis of PPID in the multivariable model highlighting the importance of this clinical sign. There were no routine haematological or biochemical variables supportive of a diagnosis of PPID.

Manufacturers' addresses

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References

a Coulter Corp., Miami, Florida, USA.

b Olympus American Inc., Diagnostic Systems Division, Melville, New York, USA.

c VETPATH Laboratory Services, Ascot, Western Australia.

d Euro Diagnostica, Malmö, Sweden.

Sources of funding

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References

The authors gratefully acknowledge the support of the University of Queensland's internal grant scheme in funding this study.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Manufacturers' addresses
  8. Authors' declaration of interests
  9. Sources of funding
  10. References
  • 1
    Schott, H.C. (2002) Pituitary pars intermedia dysfunction: equine Cushing's disease. Vet. Clin. N. Am.: Equine Pract. 18, 237-270.
  • 2
    Saiardi, A. and Borrelli, E. (1998) Absence of dopaminergic control on melanotrophs leads to Cushing's-like syndrome in mice. Mol. Endocrinol. 12, 1133-1139.
  • 3
    McFarlane, D. (2007) Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease. Ageing Res. Rev. 6, 54-63.
  • 4
    McFarlane, D. and Cribb, A. (2004) 3-nitrotyrosine accumulation and increased alpha-synuclein expression in horses with pituitary pars intermedia dysfunction (PPID.). Free Radic. Biol. Med. 37, S161.
  • 5
    McFarlane, D., Dybdal, N., Donaldson, M.T., Miller, L. and Cribb, A.E. (2005) Nitration and increased alpha-synuclein expression associated with dopaminergic neurodegeneration in equine pituitary pars intermedia dysfunction. J. Neuroendocrinol. 17, 73-80.
  • 6
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