Talk about cushing’s disease

Prevalence and aetiopathology

Equine Cushing’s Disease, also known as Pars Pituitary Intermedia Dysfunction (PPID), is the most common endocrine disorder in older horses and ponies.1 Some estimates suggest that over 15% of horses and ponies over 15 years of age are affected.2 The average age that a horse is diagnosed with PPID is 19 years and the disease is rarely seen in those less than 10-yearsold. PPID occurs as a result of neurones in the hypothalamus undergoing progressive oxidative degeneration. In the normal horse, these neurones secrete the neurotransmitter dopamine which diffuses into the adjacent pars intermedia of the pituitary gland, where it has an inhibitory effect on pars
intermedia hormone secretion. In horses and ponies suffering from PPID, dopamine secretion is reduced, resulting in excessive
hormone production from the pars intermedia, and hyperplasia of the gland. Principal among these excessive secretions is the precursor peptide proopiomelanocortin (POMC) which is cleaved into other peptide hormones including adrenocorticotropic hormone (ACTH), β-endorphin, α- melanocyte stimulating hormone (α- MSH) and corticotropin-like intermediate peptide (CLIP). These peptides have both direct effects, resulting in the clinical signs associated with the disease, and the ability to potentiate the effects of ACTH.

Clinical signs and laminitis

Horses suffering from PPID demonstrate variable and often nonspecific clinical signs, including lethargy, weight redistribution, hyperhidrosis, increased susceptibility to and recurrence of infection, ncreased parasite burden and PU/PD. Hirsutism – abnormal hair coat or delayed shedding – is perhaps the most readily identifiable change associated with PPID, and is pathognomonic for the disease. Evidence suggests that owner-identified coat changes are amongst the most reliable indicators of the presence of PPID. Clinicians readily recognise that horses and ponies with PPID are at increased risk of developing laminitis; however, new research suggests that over 80% of horses presenting with laminitis in a first opinion setting have an underlying endocrine disorder such as PPID or Equine Metabolic
Syndrome.3 This would suggest that routine screening of laminitic cases for PPID/EMS may improve early detection, intervention and outcome for these cases.

Diagnosis

The early clinical signs of PPID are often insidious in onset, vague and non-specific, potentially hampering the potential maximum benefit gained by early diagnosis and intervention.
Blood testing is an increasingly sensitive and popular tool for detection of the disease; however, many horses with clinical signs, including recurrent laminitis, still go undiagnosed. Two approaches to diagnostic testing are widely used in the UK. The endogenous ACTH assay utilises a single blood sample to assess serum ACTH levels – where abnormally high levels of ACTH indicate the presence of disease. The low-dose dexamethasone
suppression test involves two blood samples being taken immediately before and 20 hours after injection of i/v dexamethasone to assess plasma cortisol level response to challenge. Some clinicians have expressed concerns over injecting already laminitic horses with dexamethasone, although it is not possible to make an evidence-based assessment of whether this represents a genuine and significant risk. Both tests have relatively high sensitivity and specificity for PPID. In the past, the effects of seasonality have been thought to render both approaches unreliable as diagnostic indicators through the autumn months in the Northern Hemisphere. A recent publication4 has, however, put forward seasonally-adjusted
reference ranges for endogenous ACTH, suggesting that with adjusted ranges, the sensitivity and specificity of endogenous ACTH test is further improved, making this an even more useful diagnostic tool

Treatment and management

PPID is a progressive and degenerative disease. Treatment of affected horses centres on dealing with any immediate medical
problems (e.g. laminitis, infection), together with seeking to address the underlying endocrine problem. A number of therapeutic approaches have been suggested for PPID, but to date only one has gained a licence as a treatment for PPID. Prascend (pergolide mesylate, Boehringer Ingelheim) is a dopaminergic agonist indicated for the treatment of clinical signs associated with PPID, effectively “topping up” endogenous dopamine, and in so doing reducing secretion of POMC and its derivative peptides from the pars intermedia. As most horses and ponies with PPID are over 15 years of age, many may be suffering age-related comorbidities in addition to the clinical signs associated with the disease. It is therefore important that
owners instigate a good programme of routine preventive healthcare, including regular worming, dentistry and foot care, whilst feeding a high quality forage-based diet.

1. Donaldson et al (2004) Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitis. JAVMA 224 (7).
2. McGowan (2003) Diagnostic and management protocols for Equine Cushing’s Syndrome. In Practice Nov/Dec.
3. Karikoskia et al (2011) The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first opinion/referral equine hospital. Domestic animal endocrinology.
4. Durham and Coppas (2011) Equine Veterinary Journal: in press.