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Pituitary pars intermedia dysfunction (PPID)

pequis

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.
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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 horsesDomest Anim Endocrinol 50, 14-25 PubMed.
  • McFarlane D, Hill K & Anton J (2015) Neutrophil function in healthy aged horses and horses with pituitary dysfunctionVet Immunol Immunop 165 (3-4), 99-106 PubMed.
  • Karikoski N P et al (2015) Lamellar pathology in horses with pituitary pars intermedia dysfunctionEquine 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 dysfunctionEquine 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 dysfunctionEquine 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 horsesJ 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 hospitalDomest 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 dysfunctionJAVMA 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 dysfunctionJ 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 therapyPferdeheilkunde 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 diseaseAging Res Rev (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 with Cushing's disease. Equine Vet J 36 (3), 226-229 PubMed.
  • Donaldson M T, Jorgensen A J & Beech J (2004) Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitisJAVMA 224 (7), 1123-1127 PubMed.
  • McGowan C M & Neiger R (2003) Efficacy of trilostane for the treatment of equine Cushing's syndrome. Equine Vet J 35 (4), 414-418 PubMed.
  • Dacre K J P, Pirie R S, Scudamore C & Prince D R (2003) Hyperlipaemia and pancreatitis in a pony with Cushing's disease. Equine Vet Educ 15 (4), 175-178 VetMedResource.
  • McCue P M (2002) Equine Cushing's diseaseVet Clin North Am Equine Pract 18 (3), 533-543 PubMed.
  • Perkins G A, Lamb S, Erb H N et al (2002) Plasma adrenocorticotropin (ACTH) concentrations and clinical response in horses treated for equine Cushing's disease with cyprohepatdine or pergolide. Equine Vet J 34 (7), 679-685 PubMed.
  • Donaldson M T, LaMonte B H, Morresey P et al (2002) Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing's disease). J Vet Intern Med 16 (6), 742-746 PubMed.
  • Chandler K J & Dixon R M (2002) Urinary cortisol:creatinine ratios in healthy horses and horses with hyperadrenocorticism and non-adrenal disease. Vet Rec 150 (25), 773-776 PubMed.
  • Schott H C II et al (2002) Pituitary pars intermedia dysfunction: equine Cushing's diseaseVet Clin North Am Equine Pract 18 (2), 237-270 PubMed.
  • Reeves H J, Lees R & McGowan C M (2001) Measurement of basal serum insulin concentration in the diagnosis of Cushing's disease in ponies. Vet Rec 149 (15), 449-452 PubMed.
  • Van der Kolk J H et al (2001) Salivary and plasma concentration of cortisol in normal horses and horses with Cushing's disease. Equine Vet J 33 (2), 211-213 PubMed.
  • Van der Kolk J H, Ijzer J, Overgaauw P A M & van der Linde-Sipeman S J (2001) Pituitary-independent Cushing's syndrome in a horse. Equine Vet J 33 (1), 110-112 PubMed.
  • Irvine C H G & Alexander S L (1997) A novel technique for measuring hypothalamic and pituitary hormone secretion rates from collection of pituitary venous effluent in the normal horse. J Endocrinol 113, 183-192 PubMed.
  • Van der Kolk J H (1997) Equine Cushing's disease. Equine Vet Educ (4), 209-214 VetMedResource.
  • Love S & Murfy D J (1996) Diagnosis and treatment of equine pituitary adenoma (Cushing's disease). Vet Ann 36, 302-308 PubMed.
  • Munoz M C, Doreste F, Ferrer O et al (1996) Pergolide treatment for Cushing's syndrome in a horse. Vet Rec 139 (2), 41-43 PubMed.
  • Dybal N O et al (1994) Diagnostic testing for pituitary pars intermedia dysfunction in horses. JAVMA 204, 627-632 PubMed.
  • Love S (1993) Equine Cushing's disease. Brit Vet J 149 (2), 139-153 PubMed.
  • Van der Kolk J H, Kalsbeek H C, Vangarderen E et al (1993) Equine pituitary neoplasia - a clinical report of 21 cases (1990-1992). Vet Rec 133 (24), 594-597 PubMed.
  • Corke M J (1992) The pathogenesis of cutaneous signs in endocrine disease. Equine Vet Educ (3), 127-130 WileyOnline.

Other sources of information

  • Slater D, Hall J & Barrelet A (2004) Diagnosis and Management of Equine Cushing's Disease. In: Proc 43rd BEVA Congress. Equine Vet J Ltd, UK. pp 165-166.
  • McFarlane D, Donaldson M T, Saleh T M & Cribb A E (2003) The Role of Dopaminergic Neurodegeneration in Equine Pituitary Pars Intermedia Dysfunction (Equine Cushing's Disease). In: Proc 49th AAEP Convention. pp 233-237.
  • Schott H C II et al (2001) The Michigan Cushing's Project. In: Proc 47th AAEP Convention. pp 22-24.

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