Hyperadrenocorticism in Cats (Felis) | Vetlexicon
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ISSN 2398-2950


  • Syndrome resulting from excessive production of glucocorticoids.
  • Rare endocrine disease in cats (cf dogs).
  • Cause:
    • Pituitary dependent: excessive ACTH production in pituitary gland - 75% of cases.
    • Adrenal dependent: autonomous excessive corticosteroid production in adrenal gland - 25% of cases.
  • Signs: polydipsia, polyuria, polyphagia, alopecia, insulin-resistant diabetes mellitus, skin thinning and tearing.
  • Diagnosis: screening lab tests and dynamic tests of adrenal function.
  • Treatment: medical (trilostane) or surgery (adrenalectomy).
  • Prognosis: poor without treatment.
    Print out the Owner factsheet on Cushing's Disease (hyperadrenocorticism) Cushing's disease (hyperadrenocorticism)  to give to your client.

Presenting signs

  • Usually present with diabetes mellitus Diabetes mellitus, which may be insulin-resistant.
  • Polyuria/polydipsia.
  • Polyphagia.

Acute presentation

  • Sudden death due to cardiomyopathy or thromboembolism Thromboembolism: aorta secondary to glucocorticoid excess.

Age predisposition

  • Middle to old age (majority >10 years old).

Cost considerations

  • Can be quite expensive to treat and requires life-long therapy and monitoring.

Special risks

  • Poor wound healing. If possible, avoid surgery until stabilized.
    Skin extremely fragile  Hyperadrenocorticism: thinning skin   →  handling and grooming can cause tearing/sloughing.



Either Failure of negative feedback on ACTH release  →  pituitary dependent.
Or Failure of response to reduced ACTH release  →  adrenal dependent.
  • Functional pituitary tumor.
  • Functional adrenal tumor - usually unilateral with 60% adenomas and 40% carcinomas.
  • Iatrogenic HAC, because of prolonged progestogen or corticosteroid therapy reported but rare.


  • Often clinical signs at presentation, eg polydipsia/polyuria and polyphagia relate to diabetes mellitus rather than glucocorticoid excess per se.
  • Glucocorticoids profoundly affect carbohydrate, protein and fat metabolism.
  • Glucocorticoids also modify inflammatory and immune responses.
  • Excessive glucocorticoids cause:


  • Increased gluconeogenesis.
  • Increased glycogen stores.


  • Peripheral insulin resistance   →   increased insulin production initially   →   subsequent beta-cell exhaustion and cell death   →   diabetes mellitus.
  • Alternatively, glucose toxicity   →   decreased insulin secretion   →   diabetes mellitus.


  • Increased protein catabolism   →   muscle wasting and weakness.


  • Direct catabolic effect on bone matrix   →   increased urinary calcium excretion and inhibition of vitamin D action.
  • Glucocorticoids   →   negative calcium balance   →   increased PTH   →   osteoporosis.


  • Hyperkeratosis, loss of collagen, atrophy of hair follicles, disturbed protein metabolism   →   thin skin   Hyperadrenocorticism: thinning skin  , poor wound healing, poor scar formation, cessation of hair growth.


  • Leucocytosis.
  • Decrease in circulating lymphocytes and eosinophils.
  • Increase in circulating neutrophils and monocytes.


  • Interference with ADH release or action   →   polyuria   →   polydipsia.
  • Osmotic diuresis because of hyperglycemia.
  • Increased calcium excretion.

Immune system

  • Reduced inflammatory response.
  • Reduced immune response.


  • Increased lipolysis.
  • Redistributed fat deposits.


  • Many months   →   years.


Presenting problems

  • Polydipsia and polyuria.
  • Polyphagia - scavenge for food.
  • Fragile skin   Hyperadrenocorticism: thinning skin  .
  • Abdominal distension - 'pot belly'.
  • Lethargy.
  • Poor coat condition.

Client history

  • Insidious onset of skin disease and PU/PD over many months or years.

Clinical signs

  • Hepatomegaly - palpable.
  • Muscle wasting/weakness.
  • Skin: thin, dry, inelastic, striae, superficial veins visible, comedones, excessive bruising, poor wound healing, breakdown of scars, persistent infections   Hyperadrenocorticism: thinning skin .
    Thin skin can result in tearing even with routine handling.
  • Diffuse non-pruritic alopecia affecting flanks and trunk first   Skin: alopecia - endocrine 01    Skin: alopecia - endocrine 02    Skin: alopecia - endocrine 03 .
  • Hair becomes finer and brittle.

Diagnostic investigation

2-D Ultrasonography

  • Liver for size and metastases   Liver: normal - ultrasound .
  • Adrenal glands to identify uni-bilateral enlargement.


ACTH stimulation test

  • Excessive cortisol response to ACTH administration  ACTH stimulation test .
    Basal cortisol often within normal range and not useful as discriminatory test.

Dexamethasone suppression test

  • Failure of dexamethasone to suppress endogenous cortisol production  Low-dose dexamethasone suppression test .
    Need higher dose of dexamethasone (0.1 mg/kg) than for the test in the dog.Best choice is combination of ACTH stimulation and dexamethasone suppression tests.

ACTH assay

  • To distinguish between pituitary and adrenal disease once diagnosis of hyperadrenocorticism made   ACTH assay.
  • Endogenous ACTH is low in adrenal neoplasia and high in pituitary disease.
  • Some normal cats have 'low' endogenous ACTH levels.


  • CT or MRI for assessing size of pituitary or adrenal glands   →   expensive, limited availability.

Combined dexamethasone suppression-ACTH stimulation test

  • Value of this test is controversial, although it has been used as a successful screening test to diagnose hyperadrenocorticism in the cat.
  • Cats with hyperadrenocorticism show inedequate suppression of cortisol 2-4 h after an intravenous injection of 0.1 mg/kg of dexamethasone and an exaggerated response 1-2 H after ACTH stimulation.

Endogenous ACTH determination

  • Endogenous plasma ACTH concentrations should be high in cats with PDH and low or non-detectable in cats with adrenal tumors.
  • This appears to be a useful test for distinguishing PDH from ADH in cats once the diagnosis of hyperadrenocorticism has been confirmed.




  • Abdomen:
    • Pot-bellied appearance.
    • Liver enlargement.
    • Adrenal enlargement/tumor   Adrenal: mass - radiograph lateral  .
    • Distended bladder.
  • Thorax:
    • Pulmonary edema secondary to congestive heart failure   Lung: pulmonary edema lateral radiograph  .
    • Pulmonary metastases   Lung: metastases - radiograph lateral   from adrenocortical carcinoma.
    • Pulmonary thromboembolism.
    • Myocardial enlargement.

2-D ultrasound

  • Enlarged adrenal gland (bilateral in pituitary dependent disease).


  • MRI or CT imaging of pituitary (CT less effective than MRI).

Confirmation of diagnosis

Discriminatory diagnostic features

Definitive diagnostic features

Gross autopsy findings

Pituitary-dependent hyperadrenocorticism

  • Vast majority have chromophobe adenomas, in most cases <1cm diameter (microadenomas).

Adrenal-dependent hyperadrenocorticism

  • 20-25% cases caused by benign (60%), or malignant (40%), mostly unilateral adrenal tumors.
  • Adenomas are small, well-circumscribed tumors that are not locally invasive.
  • Carcinomas are larger, locally invasive, hemorrhagic and necrotic. In the right adrenal gland they frequently invade the phrenicoabdominal vein and caudal vena cava and metastasize to the liver, lung and kidney.

Differential diagnosis


Initial symptomatic treatment

  • Majority of cases presented with diabetes mellitus and infections, (particularly of the skin)   →   initiate insulin therapy and initiate antibiotic treatment.
  • Initially may require high insulin doses to overcome the resistance but as hyperglycemia is reduced the insulin requirement may drop.

Standard treatment


  • Has been suggested as the treatment of choice for best long-term results but peri-operative morbity is significant and mortality not uncommon.
  • Technically difficult.
  • Intensive care facilities are mandatory before undertaking this operation.
  • Pre-operative stabilization often necessary, with trilostane Trilostane, ketoconazole  Ketoconazole  or metyrapone (some success has been reported with mitotane Mitotane in cats).
  • Unilateral removal for ADH   →   lifelong corticosteroid replacement, if opposite gland non-functional or absent.
  • Bilateral for PDH   →   obligatory corticosteroid replacement.
    Initiate steroid replacement during surgery in parenteral fluids/0.05 mg/kg dexamethasone   Dexamethasone , or 0.625 mg/kg/hour hydrocortisone.General risk of post-operative hypoadrenocortical crisis.


  • Trilostane  Trilostane  has been used to treat hyperadrenocorticism in cats. One series of 5 cats has been published. There were few adverse effects and the results were better than previous medical attempts to treat the condition. Results however were still poor when compared with dogs. More case experience is still needed.
  • Treatment initiated at 4 mg/kg SID or BID and dosage adjusted on the results of ACTH stimulation test.


  • Technically extremely difficult - limited availability in Europe.
  • Critical post-operative phase.

Radiation therapy

  • Radiotherapy  Radiotherapy .
  • For pituitary tumor. Endocrinological improvement may take many months if it occurs at all. More useful for reducing neurological signs associated with an expanding pituitary tumor.
  • Requires special equipment and monitoring, not widely available.


  • Ketoconazole Ketoconazole.
  • Suppresses steroidogenesis.
  • Dose: 15 mg/kg BID.
  • Essential to monitor hepatic functional throughout therapy.
    Expensive and long-term success uncertain.
  • Poor hormonal control in cats.
  • Hepatotoxicity and thrombocytopenia reported.


  • Adrenal enzyme inhibitor (50-65 mg/kg BID).
    Long-term success uncertain, drug difficult to obtain.
  • Appears to be a useful drug for presurgical stabilization of cats before adrenalectomy.


  • Mitotane Mitotane
  • Appears to be well tolerated in cats despite their sensitivity to hydrogenated hydrocarbons.
  • Frequently ineffective in controlling clinical signs of hyperadrenocorticism in cats.


Subsequent management


Post surgical corticosteroid replacement
  • Continue dexamethasone after surgery 0.5-1 mg/kg IV until cat eating, then oral prednisolone   Prednisolone, 0.5-1.0mg/kg BID  →  reduce gradually over 6-8 weeks.
  • Discontinue after unilateral adrenal excision once contralateral gland becomes functional.
  • Mineralocorticoid replacement mandatory after bilateral adrenalectomy.
    • Hydrocortisone hemisuccinate/sodium succinate IV (5 mg/kg TID).
    • Once cat is eating oral fludrocortisone, 0.02 mg/kg SID (0.1 mg/cat/day PO).
  • Long-acting insulin depending on persistence of diabetes mellitus Diabetes mellitus  →  usually normalizing with resolved hyperadrenocorticism.


  • Re-assess if symptoms reappear  →   blood glucose, electrolytes, ACTH stimulation test.




  • With appropriate treatment some animals do well.
  • Most animals die of sepsis Shock: septic if not treated.
  • Many diabetic Diabetes mellitus cats with hyperadrenocorticism become better stabilized or no longer require insulin therap  Insulin after surgical treatment of the hyperadrenocorticism. In contrast those treated with trilostane usually still require insullin. However trilostane is less risky than surgery.

Expected response to treatment

  • Within 4 weeks skin changes and infections subsiding.
  • Polydipsia/polyuria markedly improved.
  • Diabetes mellitus/insulin requirements markedly reduced or back to normal.

Further Reading


Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Boland L A & Barrs V R (2017) Peculiarities of feline hyperadrenocorticism: update on diagnosis and treatment. J Feline Med Surg 19 (9), 933-947 PubMed.
  • Neiger R, Witt A L, Noble A et al (2004) Trilostane therapy for treatment of pituitary-dependent hyperadrenocorticism in 5 cats. J Vet Intern Med 18 (2), 160-164 PubMed.
  • Hoenig M (2002) Feline hyperadrenocorticism - where are we now? J Feline Med Surg (3), 171-174 PubMed.
  • Ferasin L (2001) Iatrogenic hyperadrenocorticism in a cat following a short therapeutic course of methylprednisolone acetate. JFMS (2), 87-93 PubMed.
  • Feldman E C & Nelson R W (2000) Acromegaly and hyperadrenocorticism in cats - a clinical perspective. JFMS (3), 153-158 PubMed.
  • Rossmeisl J H Jr., Scott-Moncrieff J C, Siems J et al (2000) Hyperadrenocorticism and hyperprogesteronemia in a cat with an adrenocortical adenocarcinoma. JAAHA 36 (6), 512-517 PubMed.
  • Zimmer C, Hörauf A & Reusch C (2000) Ultrasonographic examination of the adrenal gland and evaluation of the hypophyseal-adrenal axis in 20 cats. JSAP 41 (4), 156-160 PubMed.
  • Zerbe C A (1999) The Hypothalamic-Pituitary-Adrenal Axis and Pathophysiology of Hyperadrenocorticism. Comp Contin Educ Pract Vet 21 (12), 1134-1137 VetMedResource.
  • Watson P J & Herrtage M E (1998) Hyperadrenocorticism in 6 cats. JSAP 39 (4), 175-84 PubMed.
  • Schwedes C S (1997) Mitotane (O,p'-DDD) treatment in a cat with hyperadrenocorticism. JSAP 38 (11), 520-524 PubMed.
  • Henry C J, Clark T P, Young D W et al (1996) Urine cortisol:creatinine ratio in healthy and sick cats. J Vet Intern Med 10 (3), 123-126 PubMed.
  • Duesberg C A, Nelson R W, Feldman E C et al (1995) Adrenalectomy for treatment of hyperadrenocorticism in - cats 10 cases (1988-1992). JAVMA 207 (8), 1066-1070 PubMed.
  • Nelson R W, Feldman E C & Smith M C (1988) Hyperadrenocorticism in cats - seven cases (1978-1987). JAVMA 193 (2), 245-250 PubMed.

Other sources of information

  • Helton-Rhodes K (1997) Cutaneous manifestations of hyperadrenocorticism. In: August J R (Ed)Consultations in Feline Internal Medicine 3. pp 191-198. Philadelphia, PA: W B Saunders. ISBN 0-7216-5814-8. (very good and concise discussion of specific dermatology).
  • Feldman E C & Nelson R W (1996) Hyperadrenocorticism in cats. In: Canine and Feline Endocrinology and Reproduction2nd edn. Philadelphia: W B Saunders. pp 256-261.
  • Feldman E C & Nelson R W (1991) Hyperadrenocorticism. In: August, J.R. (Ed) Consultations in Feline Internal Medicine. pp 267-270. Philadelphia, PA: W B Saunders. ISBN 0-7216-2226-7. (good review, very good discussion of therapy management).