South African Equine Veterinary Association Congress 2015 Protea Hotel Stellenbosch
Pituitary pars intermedia dysfunction - diagnosis and treatment
Schott HC*
Professor, Equine Internal Medicine
Department of Large Animal Clinical Sciences
D-202 Veterinary Medical Center
Michigan State University, East Lansing, MI 48824-1314
(517)-353-9710 [email protected]
Although the frequency of diagnosis and treatment of pituitary pars intermedia dysfunction
(PPID) in horses has clearly increased over the past decade, there is no evidence that the
prevalence of PPID is actually increasing. Increased recognition of the disease is likely a
consequence of clients maintaining their horses to more advanced ages as well as improved health
care (e.g., diet and dentistry) being provided to older horses. Recent surveys of horse owners in
Queensland, Australia and the United Kingdom revealed prevalences of 15-20% of PPID in
horses and ponies 15 years of age and older, increasing to nearly 30% in horses over 30 years of
age. There is no gender predilection and average age of affected horses is around 20 years. All
breeds and types of equids can be affected with PPID but ponies appear to be at greater risk.
Pathophysiology: In humans and dogs, Cushing‟s disease is most commonly attributed to a
corticotroph adenoma in the pars distalis of the pituitary gland. These adenomas are thought to
arise spontaneously. In contrast, Cushing‟s disease in horses is almost exclusively attributed to
melanotrope hyperplasia or adenoma formation in the pars intermedia (PI) that appears to be due
to loss of hypothalamic innervation. Abnormal PI tissue in horses contains markedly reduced
amounts of dopamine, about 10% that of normal pars intermedia tissue, consistent with a specific
loss of hypothalamic dopaminergic innervation. Further, tyrosine hydroxylase activity, the rate
limiting enzyme for production of dopamine, is also markedly reduced in equids with PPID.
Recent evidence suggests that this loss of dopaminergic innervation is due to oxidant-induced
injury to hypothalamic tissue. Thus, a risk factor for affected horses may be reduced anti-oxidant
defense mechanisms in neural tissue. Further, insoluble aggregates of the neural protein αsynuclein have been found in dopaminergic nerve terminals of PPID-affected horses. These
protein aggregates are also found in humans with Parkinson‟s disease suggesting that the two
neurodegenerative disorders may share a similar pathogenesis. However, the population of
neurons affected in horses, as compared to humans, appears to be somewhat different leading to
the difference in clinical signs observed in each species.
In normal equids, hypothalamic dopaminergic neurons exert a tonic inhibitory action on PI
melanotropes. Progressive loss of dopaminergic innervation over many years leads to unregulated
enlargement of the PI in equids with PPID, initially by melanotrope hyperplasia and progressing
to micro- and macroadenoma formation within the PI. A consequence of loss of PI dopaminergic
innervation is excess production of the prohormone pro-opiomelanocortin (POMC, 241 amino
acids). Processing of POMC by prohormone convertase 1 and prohormone convertase 2 leads to
increased amounts of many POMC-derived peptides, including ACTH1-39 (POMC138-176) and αMSH (ACTH1-13) in jugular venous plasma. Excess amounts of POMC peptides are thought to be
responsible for development of the variable clinical signs of PPID, although actual
pathophysiology remains poorly understood.
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