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Pituitary pars intermedia dysfunction (PPID)
Synonym(s): Pituitary pars intermedia dysfunction, PPID, Equine Cushing's disease, Equine Cushing's syndrome, Hyperadrenocorticism, ECD
Introduction
- Pituitary pars intermedia dysfunction (PPID) is an age-related dopaminergic neurodegenerative disease, with hyperplasia or adenoma(s) of the pars intermedia.
- Cause: loss of dopaminergic inhibition of the melanotropes of the pars intermedia, resulting in overproduction and elevated circulating pro-opiomelanocortin (POMC)-derived peptides, including a-melanocyte stimulating hormone (a-MSH), b-endorphin, corticotrophin-like intermediate peptide (CLIP), and adrenocorticotrophic hormone (ACTH).
- Signs: hypertrichosis, lethargy/depression, laminitis, epaxial muscle wastage/muscle atrophy, fat re-distribution, weight loss, sweating, polydipsia, polyuria, recurrent infections.
- Diagnosis: basal plasma ACTH, overnight dexamethasone suppression test, TRH stimulation test (of ACTH).
- Treatment: pergolide, trilostane, cyproheptadine, bromocriptine.
- Prognosis: >/=75% of cases improve clinically and endocrinologically with treatment.
Presenting signs
- Hypertrichosis (commonly described as hirsutism), delayed or partial shedding of the winter coat, or localized patches of long hair, particularly on the legs or the ventral mandible, neck or thorax.
- Laminitis Foot: laminitis.
- Lethargy or depression.
- Epaxial muscle wastage, leading to 'poor topline'.
- Weight loss Weight loss: overview.
- Fat re-distribution, including bulging supraorbital fat pads.
- Pendulous abdomen.
- Hyperhidrosis or patchy sweating.
- Increased susceptibility to infection/recurrent infections:
- Sinusitis Paranasal sinuses: bacterial sinusitis.
- Periodontal disease Teeth: periodontal disease/gingivitis.
- Dermatophilosis Dermatophilosis.
- Ringworm Dermatophytosis.
- Ectoparasites (lice Pediculosis/mites Chorioptes infestation (chorioptic mange)).
- Conjunctivitis Conjunctivitis: overview.
- Hoof abscess Foot: subsolar abscess / infection.
- Endoparasites (strongyles Strongyle infestation: large).
- Polydipsia/polyuria Polydipsia / polyuria.
- Infrequently reported clinical signs:
- Neurological signs, including seizures Epilepsy: overview, ataxia.
- Polyphagia.
- Anorexia.
- Ulceration of oral mucosa Mouth: ulcers.
- Inappropriate lactation.
- Poor fertility.
Acute presentation
- Slowly progressive - rarely an acute onset of signs.
Geographic incidence
- Worldwide.
Age predisposition
- Aged (>15 years); increasing age is the only signalment factor identified as a risk factor for PPID.
- Typically diagnosed in animals aged 18-23, with few cases reported in animals <10 years.
Breed/Species predisposition
- Case series appear to indicate greater proportions of pony breeds affected, however breed/type has not been reported as a significant risk factor.
- Ponies have a greater lifespan and are therefore over-represented with increasing age.
- Clinical signs of PPID are more frequently observed/reported in pony breeds.
Public health considerations
- In rare cases exhibiting neurological signs, riding is dangerous.
Cost considerations
- Long-term medical therapy.
- Loss of use of elderly horse.
Special risks
- Risk of infection or parasitism.
- Risk of laminitis that can be refractory to treatment if PPID is not appropriately controlled.
- Prolonged wound healing times.
Pathogenesis
Etiology
- Neurodegeneration of dopaminergic periventricular neurons that innervate the pars intermedia of pituitary gland → hypertrophy, hyperplasia and adenoma formation in the pars intermedia → proliferation of melanotropes with increased production of pro-opiomelanocortin (POMC) → elevated circulating POMC-derived peptides.
Predisposing factors
General
- Aged horse.
Pathophysiology
- PPID results from loss of dopaminergic innervation of pars intermedia.
- Neurodegeneration of dopaminergic neurons → loss of dopaminergic inhibition → hypertrophy, hyperplasia and adenoma formation in the pars intermedia → increased hormone production, including ACTH.
- Hypertrophied melanotropes produce pro-opiomelanocortin polypeptide (POMC), which is metabolized → beta-endorphins, alpha-melanocyte stimulating hormone, ACTH and corticotropin-like intermediate lobe peptide.
- In advanced cases, adenoma may compress adjacent thalamic and brain stem tissue as well as optic chiasma → CNS effects.
- Pituitary pars intermedia is not controlled by negative feedback from circulating glucocorticoids in contrast to pars distalis.
- Basal serum insulin is elevated in a proportion of PPID cases → laminitis Foot: laminitis.
Timecourse
- Usually slowly progressive, with gradual onset of signs over several years.
Epidemiology
- Prevalence of 21% in horses and ponies aged >/=15 years.
- Increasing horse age is a risk factor.
- No breed predisposition reported in epidemiological studies.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed papers
- Recent references from PubMed and VetMedResource.
- Mastroa L M, Adams A A & Urschela K L (2015) Pituitary pars intermedia dysfunction does not necessarily impair insulin sensitivity in old horses. Domest Anim Endocrinol 50, 14-25 PubMed.
- McFarlane D, Hill K & Anton J (2015) Neutrophil function in healthy aged horses and horses with pituitary dysfunction. Vet Immunol Immunop 165 (3-4), 99-106 PubMed.
- Karikoski N P et al (2015) Lamellar pathology in horses with pituitary pars intermedia dysfunction. Equine Vet J. doi: 10.1111/evj.12450 [Epub ahead of print] PubMed
- McFarlane D (2014) Pathophysiology and clinical features of pituitary pars intermedia dysfunction. Equine Vet Educ 46 (11), 592-598 VetMedResource.
- Durham A E et al (2014) Pituitary pars intermedia dysfunction: Diagnosis and treatment. Equine Vet Educ 26 (4), 216-223 VetMedResource.
- Tadros E M & Frank N (2013) Endocrine disorders and laminitis. Equine Vet Educ 25 (3), 152-162 VetMedResource.
- McGowan T W, Pinchbeck G P & McGowan C M (2013) Evaluation of basal plasma alpha-melanocyte-stimulating hormone and adrenocorticotrophic hormone concentrations for the diagnosis of pituitary pars intermedia dysfunction from a population of aged horses. Equine Vet J 45 (1), 66-73 PubMed.
- McGowan T W, Pinchbeck G P & McGowan C M (2013) Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses. Equine Vet J 45 (1), 74-79 PubMed.
- Rendle D I et al (2013) Effects of pergolide mesylate on plasma adrenocorticotropic hormone concentration in horses with pituitary pars intermedia dysfunction. Equine Vet J 45 (S44), 19 WileyOnline.
- Copas V E & Durham A E (2012) Circannual variation in plasma adrenocorticotropic hormone concentrations in the UK in normal horses and ponies, and those with pituitary pars intermedia dysfunction. Equine Vet J 44 (4), 440-443 PubMed.
- McFarlane D (2011) Equine pituitary pars intermedia dysfunction. Vet Clin North Am Equine Pract 27 (1), 93-113 VetMedResource.
- McFarlane D et al (2011) The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and ±-melanocyte-stimulating hormone plasma concentrations in horses. J Vet Intern Med 25 (4), 872-881 PubMed.
- Karikoski N P, Horn I, McGowan T W & McGowan C M (2011) The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital. Domest Anim Endocrinol 41 (3), 111-117 PubMed.
- Beech J et al (2011) 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. JAVMA 238 (10), 1305-1315 PubMed.
- Beech J, Boston R & Lindborg S (2011) Comparison of cortisol and ACTH responses after administration of thyrotropin releasing hormone in normal horses and those with pituitary pars intermedia dysfunction. J Vet Intern Med 25 (6), 1431-1438 PubMed.
- Pongratz M C, Graubner C & Eser M W (2010) Equine Cushing's Syndrome: Long-term effect of pergolide therapy. Pferdeheilkunde 26 (4), 598-603 VetMedResource.
- McFarlane D (2007) Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease. Aging Res Rev 6 (1), 54-63 PubMed.
- Orsini A J, Donaldson M T, Koch C & Boswell R (2007) Iatrogenic secondary hypoadrenocorticism in a horse with pituitary pars intermedia dysfunction (equine Cushing's disease). Equine Vet Educ 19 (2), 81-87 VetMedResource.
- Frank N et al (2006) Evaluation of the combined dexamethasone suppression/ thyrotropin-releasing hormone stimulation test for detection of pars intermedia pituitary adenomas in horses.J Vet Intern Med 2b0, 987-993 PubMed.
- Menzies Gow N (2006) Equine pituitary pars intermedia dysfunction (Equine Cushing's disease). UK Vet 11 (7), 13-17 VetMedResource.
- Pilsworth R C & Knottenbelt D C (2006) Hirsutism. Equine Vet Educ 18 (3), 120-121 VetMedResource.
- Keen J A et al (2004) Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses wit