Equine endocrine disease most often occurs in older horses as a result of dysfunction of the pituitary pars intermedia. Equine
metabolic syndrome is the name applied to the association of obesity in older horses and the risk of development of laminitis.
Horses are living longer lives and their owners are becoming more interested in preserving health, athletic function and quality
of life through the later years. There are two endocrine disorders of mature horses: equine Cushing's disease and the metabolic
syndrome. These two disorders feature some clinical similarities such as insulin resistance and chronic laminitis. However,
the pathogenesis of each disease is quite different in each case.
Equine Cushing's disease is a disorder of the pituitary gland that causes a variety of clinical signs: a long, wavy hair coat;
excessive sweating; lethargy; chronic recurrent laminitis; infertility; weight loss with muscle wasting; abnormal distribution
of fat, with accumulations in the crest of the neck, tail head, sheath and above the eyes; polyuria and polydipsia; and increased
susceptibility to infections. The disease tends to occur in middle-aged and geriatric horses.
In affected horses, the pituitary pars intermedia produces excessive amounts of pro-opiomelanocortin (POMC) from which is
cleaved adrenocorticotropic hormone (ACTH). In healthy horses, the majority of circulating ACTH comes from the pars distalis
which produces less ACTH when plasma cortisol concentrations increase (negative feedback). In contrast, function of the pars
intermedia is not influenced by cortisol concentration. Instead, production of POMC by the pars intermedia is controlled by
nerves arising from the hypothalamus. Dopamine and serotonin serve as the neurotransmitters. Horses with equine Cushing's
disease have increased concentrations of dopamine in the pars intermedia causing increased production of POMC and in turn
ACTH. The ACTH increases the amount of cortisol produced by the adrenal gland; this cortisol does not reduce the amount of
ACTH produced by the pars intermedia. In contrast, serotonin released by hypothalamic nerves does reduce pars intermedia production
of POMC. Therefore, treatment of equine Cushing's disease involves inhibiting the excess dopamine or increasing the concentrations
of inhibitory serotonin (or both).
Identification of compatible clinical signs is an important aspect of diagnosis of Cushing's disease. The long, wavy hair
coat (hirsuitism) is characteristic and fairly specific for this disease. However, diagnosis of earlier requires endocrinology
tests. The dexamethasone suppression test is the most accurate method of diagnosis. A basal plasma sample (usually in heparin)
is collected for cortisol measurement after which dexamethasone is administered by intramuscular injection (0.04 mg/kg). The
post treatment samples can be collected at various intervals after dexamethasone treatment; however, the most important samples
are collected at 16-18 hours (to confirm that suppression occurred) and at 24 hours (to confirm that suppression was sustained).
The most sensitive use of dexamethasone suppression testing uses these two samples. Because horses with Cushing's disease
are under pars intermedia control, they do not adequately suppress during dexamethasone suppression testing. Less sensitive
tests for Cushing's disease includes ACTH sampling and Thyrotropin releasing hormone (TRH) testing. Measurement of plasma
ACTH involves collection and analysis of a single blood sample; the pituitary gland in affected horses often secretes excessive
amounts of ACTH into the bloodstream as compared to normal horses. Blood samples must be handled very carefully to avoid degradation
of ACTH and falsely low measured values. Stress and pain due to other conditions may also result in falsely elevated values.
Most importantly, horses with Cushing's disease do not keep elevated ACTH concentration 24 hours a day every day so false
negative results often occur. TRH testing involves administering TRH and collecting blood samples to test for cortisol measurement.
TRH increases cortisol production in Cushing's horses but not in healthy horses. This test only requires a few hours to complete
but some horses with Cushing's disease will have normal test results. Supplemental tests that may be useful in suspect cases
include measurements of blood glucose and insulin. Some affected horses are insulin resistant and this may impact development
Optimal management of Cushing's disease involves a combination of both specific medication to normalize the function of the
pituitary gland and supportive care to address and prevent complications associated with the disease. Specific endocrine therapy
manages the disease but is not curative necessitating life-long management. In the early stages, specific medication may not
be required and conservative measures such as body clipping to remove the long hair coat, strict attention to diet, and scrupulous
attention to teeth, hooves and preventive care may be sufficient to provide good quality of life. Diagnosis and aggressive
treatment of bacterial infections is important. Since affected horses are often insulin resistant, sweet feed and other feedstuffs
high in soluble carbohydrates should be avoided while fiber and fat are emphasized. Pelleted or extruded feeds designed specifically
for older horses are strongly recommended.