Equis ISSN 2398-2977

Pituitary: adenoma

Synonym(s): Pituitary pars intermedia dysfunction, PPID, Equine Cushing's disease, Equine Cushing's syndrome, Hyperadrenocorticism, ECD

Contributor(s): Sarah Binns, Christopher Brown, Prof Derek Knottenbelt, Prof Jonathon Naylor, Tim Watson, Jo Ireland

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 peptieds, 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.
Print off the Owner factsheets on Caring for the older horse and Equine Cushing's disease to give to your clients.

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   →    hypertorphy, 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, adrenocorticotrophic hormine (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

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Treatment

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Prevention

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Outcomes

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

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 Endocrinol50, 14-25PubMed.
  • McFarlane D, Hill K & Anton J (2015) Neutrophil function in healthy aged horses and horses with pituitary dysfunction.Vet Immunol Immunop165(3-4), 99-106PubMed.
  • Karikoski N Pet 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 Educ46(11), 592-598VetMedResource.
  • Durham A Eet al(2014)Pituitary pars intermedia dysfunction: Diagnosis and treatment.Equine Vet Educ26(4), 216-223VetMedResource.
  • Tadros E M & Frank N (2013)Endocrine disorders and laminitis.Equine Vet Educ25(3), 152-162VetMedResource.
  • 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 J45(1), 66-73PubMed.
  • 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 J45(1), 74-79PubMed.
  • 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 J44(4), 440-443PubMed.
  • McFarlane Det 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 Med25(4), 872-881PubMed.
  • 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 Endocrinol41(3), 111-117PubMed.
  • Beech Jet 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.JAVAM238(10), 1305-1315PubMed.
  • 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 Med25(6), 1431-1438PubMed.
  • Pongratz M C, Graubner C & Eser M W (2010)Equine Cushing's Syndrome: Long-term effect of pergolide therapy.Pferdeheilkunde26(4), 598-603VetMedResource.
  • McFarlane D (2007)Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease.Aging Res Rev6(1), 54-63PubMed.
  • 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 Educ19(2), 81-87VetMedResource.
  • Frank Net 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 Med2b0, 987-993PubMed.
  • Menzies Gow N (2006)Equine pituitary pars intermedia dysfunction (Equine Cushing's disease).UK Vet11(7), 13-17VetMedResource.
  • Pilsworth R C & Knottenbelt D C (2006)Hirsutism.Equine Vet Educ18(3), 120-121VetMedResource.
  • Keen J Aet al(2004)Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with Cushing's disease.Equine Vet J36(3), 226-229PubMed.
  • Donaldson M T, Jorgensen A J & Beech J (2004)Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitisJAVMA224(7), 1123-1127PubMed.
  • McGowan C M & Neiger R (2003)Efficacy of trilostane for the treatment of equine Cushing's syndrome.Equine Vet J35(4), 414-418PubMed.
  • 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 Educ15(4), 175-178VetMedResource.
  • Perkins G A, Lamb S, Erb H N, Schanbacher B, Nydam D V & Divers T J (2002)Plasma adrenocorticotropin (ACTH) concentrations and clinical response in horses treated for equine Cushings disease with cyprohepatdine or pergolide.Equine Vet J34(7), 679-685PubMed.
  • Donaldson M T, LaMonte B H, Morresey P, Smith G & Beech J (2002)Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushings disease).J Vet Intern Med16(6), 742-746PubMed.
  • Chandler K J & Dixon R M (2002)Urinary cortisol:creatinine ratios in healthy horses and horses with hyperadrenocorticism and non-adrenal disease.Vet Rec150(25), 773-776PubMed.
  • Reeves H J, Lees R & McGowan C M (2001)Measurement of basal serum insulin concentration in the diagnosis of Cushings disease in ponies.Vet Rec149(15), 449-452PubMed.
  • Van der Kolk J Het al(2001)Salivary and plasma concentration of cortisol in normal horses and horses with Cushing's disease.Equine Vet J33(2), 211-213PubMed.
  • 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 J33(1), 110-112PubMed.
  • 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 Endocrinol113, 183-192PubMed.
  • Van der Kolk J H (1997)Equine Cushing's disease.Equine Vet Educ9(4), 209-214VetMedResource.
  • Love S & Murfy D J (1996)Diagnosis and treatment of equine pituitary adenoma (Cushing's disease).Vet Ann36, 302-308PubMed.
  • Munoz M C, Doreste F, Ferrer Oet al(1996)Pergolide treatment for Cushing's syndrome in a horse.Vet Rec139(2), 41-43PubMed.
  • Dybal N Oet al(1994)Diagnostic testing for pituitary pars intermedia dysfunction in horses.JAVMA204, 627-632PubMed.
  • Love S (1993)Equine Cushing's disease.Brit Vet J149(2), 139-153PubMed.
  • Van der Kolk J H, Kalsbeek H C, Vangarderen Eet al(1993)Equine pituitary neoplasia - a clinical report of 21 cases (1990-1992).Vet Rec133(24), 594-597PubMed.
  • Corke M J (1992)The pathogenesis of cutaneous signs in endocrine disease.Equine Vet Educ4(3), 127-130WileyOnline.

Other sources of information

  • Rendle D Iet al (2013)Effects of pergolide mesylate on plasma adrenocorticotropic hormone concentration in horses with pituitary pars intermedia dysfunction.Equine Vet J45(S44), 19WileyOnline.
  • McFarlane D (2011)Equine pituitary pars intermedia dysfunction. Vet Clin North Am Equine Pract27(1), 93-113VetMedResource.
  • McCue P M (2002)Equine Cushings disease.Vet Clin North Am Equine Pract18(3), 533-543PubMed.
  • Schott H C 2nd et al(2002)Pituitary pars intermedia dysfunction: equine Cushings disease.Vet Clin North Am Equine Pract18(2), 237-270PubMed.
  • Slater D, Hall J & Barrelet A (2004)Diagnosis and Management of Equine Cushing's Disease. In:Proc 43rd BEVA Congress. Equine Vet J Ltd, Newmarket. 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 2ndet al(2001)The Michigan Cushings Project. In:Proc 47th AAEP Convention. pp 22-24.


ADDED