ISSN 2398-2969      



Synonym(s): Cushing's syndrome, HAC


  • Relatively common endocrine disease.
  • Cause: syndrome resulting from excessive production or administration of glucocorticoids.
  • Signs: polydipsia, polyuria, polyphagia, alopecia, lethargy.
  • Diagnosis: screening lab tests and dynamic tests of adrenal function.
  • Treatment: trilostane, mitotane.
  • Prognosis: good with adequate monitoring.
    Print out owner factsheet on Cushing's disease (hyperadrenocorticism) Cushing's disease (hyperadrenocorticism) to give to your client.



  • Iatrogenic associated with prolonged corticosteroid therapy.
  • For pathophysiology see adrenal pathophysiology Adrenal: anatomy and physiology.
  • Failure of negative feedback on ACTH release.
  • Functional pituitary tumor (corticotrophic adenoma).
  • Functional adrenal tumor - usually unilateral with 50% benign, 50% malignant.


  • Glucocorticoids profoundly affect carbohydrate, protein and fat metabolism.
  • Glucocorticoids also modify inflammatory and immune responses.
  • Excessive glucocorticoids cause:


  • Increased gluconeogenesis.
  • Increased glycogen stores.
  • Induce certain enzymes.


  • Increased protein catabolism → muscle wasting and weakness.


  • Microscopic osteopenia associated with increased PTH, increased protein catabolism and negative calcium balance. Dogs with hyperadrenocorticism do not get clinically detectable osteoporosis (cf humans).


  • Increased protein catabolism → thin skin, poor wound healing, poor scar formation, cessation of hair growth.


  • Erythrocytosis.
  • Decrease in circulating lymphocytes and eosinophils.
  • Increase in circulating neutrophils.


  • Increased glomerular filtration rate or interference with ADH release or action → polyuria → polydipsia.
  • Increased calcium excretion.

Immune system

  • Reduced inflammatory response.
  • Reduced immune response.


  • Increased lipolysis.
  • Redistributed fat deposits.

Genital system

  • Reduced gonadotrophins → anestrus in bitch/testicular atrophy in dog.


  • Months → years.


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Further Reading


Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Ramsey I & Ristic J (2007) Diagnosis of canine hyperadrenocorticism. In Practice 29 (8), 446-454 VetMedResource.
  • Ramsey I & Neiger R (2007) Treatment of canine hyperadrenocorticism. In Practice 29 (9), 512-519 VetMedResource.
  • Bell R, Neiger R, McGrotty Y & Ramsey I K (2006) Study of the effects of once daily trilostane administration on cortisol concentrations and ACTH responsiveness in hyperadrenocorticoid dogs. Vet Rec 159 (9), 277-281 PubMed.
  • Ramsey I (2006) Treatment of canine hyperadrenocorticism. UK Vet 11 (2), 27-32 VetMedResource.
  • Ramsey I (2006) Diagnosis of canine hyperadrenocorticism. UK Vet 11 (1), 21-28 MAGOnlineLibrary.
  • Ramsey I (2006) Pathophysiology of hyperadrenocorticism. UK Vet 10 (8), 31-37.
  • Barker E, Campbell S, Tebb A, Neiger R, Herrtage M E & Ramsey I K (2005) A comparison of the survival times of dogs treated for hyperadrenocorticism with trilostane or mitotane. J Vet Intern Med 19 (6), 810-815 PubMed.
  • Ramsey I K, Tebb A, Harris E, Evans H & Herrtage M E (2005) Hyperparathyroidism in dogs with hyperadrenocorticism. JSAP 46 (11), 531-536 PubMed.
  • Tebb A J, Arteaga A, Evans H & Ramsey I K (2005) Canine hyperadrenocorticism: effects of trilostane on parathyroid hormone, calcium and phosphate concentrations. JSAP 46 (11), 537-542 PubMed.
  • Wenger M, Sieber-Ruckstuhl N S, Muller C & Reusch C E (2004) Effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism. Am J Vet Res 65 (9), 1245-1250 PubMed.
  • Neiger R (2003) Treatment of canine hyperadrenocorticism (Cushing's Disease) with trilostane. UK Vet (2) 19-22.
  • Neiger R, Ramsey I K, O'Connor J, Hurley K & Mooney C T (2002) Trilostane treatment of 78 dogs with pituitary dependent hyperadrenocorticism. Vet Rec 150 (26), 799-804 PubMed.
  • Ruckstuhl N S, Nett C S & Reusch C E (2002) Results of clinical examinations, laboratory tests, and ultrasonography in dogs with pituitary-dependent hyperadrenocorticism treated with trilostane. Am J Vet Res 63 (4), 506-512 PubMed.
  • Gould S M, Baines E A, Mannion P A, Evans H & Herrtage M E (2001) Use of endogenous ACTH concentration and adrenal ultrasonography to distinguish the cause of canine hyperadrenocorticism. JSAP 42 (3), 113-121 PubMed.
  • Frank L A, DeNovo R C, Kraje A C et al (2000) Cortisol concentrations following stimulation of healthy and adrenopathic dogs with two doses of tetracosactrin. JSAP 41 (7), 308-311 PubMed.
  • Reusch C E, Steffen T & Hoerauf A (1999) The efficacy of L-Deprenyl in dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 13 (4), 291-301 PubMed.
  • Zerbe C A et al (1999) The Hypothalamic-Pituitary-Adrenal Axis and Pathophysiology of Hyperadrenocorticism. Comp Contin Educ Pract Vet 21 (12), 1134-1137 VetMedResource.
  • Hess R S, Kass P H & Ward C R (1998) Association between hyperadrenocorticism and development of calcium-containing uroliths in dogs with urolithiasis. JAVMA 212 (12), 1889-1891 PubMed.
  • Théon A P & Feldman E C (1998) Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs. JAVMA 213 (2), 225-231 PubMed.
  • Thuróczy J, van Sluijs F J, Kooistra H S et al (1998) Multiple endocrine neoplasms in a dog - corticotrophic tumor, bilateral adrenocortical tumors, and pheochromocytoma. Vet Q 20 (2), 56-61 VetMedResource.
  • Angles J M, Feldman E C, Nelson R W et al (1997) Use of urine cortisol-creatinine ratio versus adrenocorticotropic hormone stimulation testing for monitoring mitotane treatment of pituitary-dependent hyperadrenocorticism in dogs. JAVMA 211 (8), 1002-1004 PubMed.
  • Dunn K J (1996) Complications associated with the diagnosis and management of canine hyperadrenocorticism. In Practice 19 (5), 246-52 VetMedResource.
  • Grooters A M, Theisen S K et al (1996) Ultrasonographic characteristics of the adrenal glands in dogs with PDH - comparison with normal dogs. JVIM 10 (3), 110-115 PubMed.
  • Bertoy E H, Feldman E C, Nelson R Wet al (1995) MRI of the brain of dogs with recently diagnosed but untreated pituitary dependent hyperadrenocorticism. JAVMA 206 (5), 651-656 PubMed.
  • van Sluijs F J, Sjollema B E, Voorhout G, van der Ingh T S G A M & Rijnberk A (1995) Results of adrenalectomy in 36 dogs with hyperadrenocorticism​ caused by adrenocortical tumor. Vet Q 17 (3), 113-116 PubMed.
  • Kintzer P P & Peterson M E (1994) Mitotane treatment of 32 dogs with cortisol-secreting adrenocortical neoplasms. JAVMA 205 (1), 54-61 PubMed.
  • Kintzer P P & Peterson M E (1991) Mitotane (o,p'-DDD) treatment of 200 dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 5 (3), 182-190 PubMed.

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ACTH stimulation test

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Blood biochemistry: alkaline phosphatase (ALP)

Blood biochemistry: bile acid stimulation test

Blood biochemistry: cholesterol

Blood biochemistry: glucose

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Computed tomography

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Diabetes insipidus: nephrogenic

Diabetes mellitus

Diabetes mellitus: complications of treatment

Diabetes mellitus: pathophysiology

Ear: aural hematoma


Hematology: eosinophil

Hematology: lymphocyte

Hemostatic disorder: acquired

High-dose dexamethasone suppression test

Hypercalcemia: overview


Hyperosmolar hyperglycemic state




Intracranial hemorrhage


Kidney: pyelonephritis

Kidney: thromboembolism

Liver function assessment

Liver: steroid hepatopathy

Low-dose dexamethasone suppression test

Lung: pulmonary thromboembolism

Magnetic resonance imaging: brain



Myotonic myopathy (myotonia)


Nutritional secondary hyperparathyroidism


Pancreatitis: acute

Perianal neoplasia

Pituitary adenoma

Pituitary gland: neoplasia

Polyuria/polydipsia (PU/PD)

Poodle: Miniature

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Radiography: abdomen

Radiography: thorax

Radiology: liver

Radiology: lungs


Retina: sudden acquired retinal degeneration syndrome

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Skin: acral lick granuloma

Skin: alopecia - overview

Skin: alopecia X

Skin: candidiasis

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Skin: deep folliculitis and furunculosis

Skin: deep pyoderma

Skin: demodectic mange

Skin: hyperandrogenism

Skin: hyperestrogenism

Skin: hypoandrogenism

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Yorkshire Terrier

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