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Also known as: '''''Cushings Disease'''''

Also known as: '''''Cushings Disease'''''

[[Image:Nodular hyperplasia.jpg|thumb|right|200px|<small><center><b>Adrenal Nodular Hyperplasia</b>. Courtesy of A. Jefferies</center></small>]]  

[[Image:Nodular hyperplasia.jpg|thumb|right|200px|<small><center><b>Adrenal Nodular Hyperplasia</b>. Courtesy of A. Jefferies</center></small>]]  

[[Image:Adrenal neoplasia.jpg|thumb|right|200px|<small><center><b>Adrenal Neoplasia</b>. Courtesy of A. Jefferies</center></small>]]

[[Image:Adrenal neoplasia.jpg|thumb|right|200px|<small><center><b>Adrenal Neoplasia</b>. Courtesy of A. Jefferies</center></small>]]

[[Image:Mitotane therapy.jpg|thumb|right|200px|<small><center><b>Post-Mitotane Therapy</b>. Courtesy of A. Jefferies</center></small>]]  

[[Image:Mitotane therapy.jpg|thumb|right|150px|<small><center><b>Post-Mitotane Therapy</b>. Courtesy of A. Jefferies</center></small>]]  

Hyperadrenocorticism is a common disease of adrenal hyperfunction that is seen most commonly in the dog. There are three known causes of the adrenal hyperfunction: dysfunction of the pituitary gland, dysfunction of the adrenal glands and iatrogenic administration of corticosteroids.  

Hyperadrenocorticism is a common disease of adrenal hyperfunction that is seen most commonly in the dog. There are three known causes of the adrenal hyperfunction: dysfunction of the pituitary gland, dysfunction of the adrenal glands and iatrogenic administration of corticosteroids.  

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Grossly the adrenals have an irregular surface with protruding nodules of cortical tissue; the hyperplased zona fasciculata cells.  

Grossly the adrenals have an irregular surface with protruding nodules of cortical tissue; the hyperplased zona fasciculata cells.  

===Adrenal Dependant Hyperadrenocorticism===

===Adrenal Dependant Hyperadrenocorticism===

== Diagnosis ==

== Diagnosis ==

'''Clinical pathology''' results may lead to an indicative diagnosis. Roughly 85- 95% of cases will show lymphocytopenia and eosinopenia and marked elevation of plasma alkaline phosphatase (ALP). Hypercholoesterolaemina has also been identified in 90% of dogs with this condition. Hyperglycaemia and hypernatraemia are sometimes noted, as is an increased urinary cortisol: creatinine ratio.

'''Clinical pathology''' results may lead to an indicative diagnosis. Roughly 85 - 95% of cases will show [[Lymphopenia|lymphocytopenia]] and [[eosinopenia]] and marked elevation of plasma alkaline phosphatase (ALP). Hypercholoesterolaemia has also been identified in 90% of dogs with this condition. Hyperglycaemia and hypernatraemia are sometimes noted, as is an increased urinary cortisol : creatinine ratio.

 

'''Liver cytology''': will show cytoplasmic vacuolation of hepatocytes consistent with the glycogen accumulation seen in steroid hepatopathies. A PAS stain can be used to identify the glycogen, which will stain bright pink.

Other specific diagnostic procedures include: '''ACTH Stimulation test''': measure cortisol before and 30-60 mins after i/v ''Synacthen'' administration. A positive result is initially high cortisol followed by a markedly elevated cortisol after stimulation (>600nmol/l).  

Other specific diagnostic procedures include: '''ACTH Stimulation test''': measure cortisol before and 30-60 mins after i/v ''Synacthen'' administration. A positive result is initially high cortisol followed by a markedly elevated cortisol after stimulation (>600nmol/l).  

Adrenal dependant disease may be unresponsive to ACTH.  

Adrenal dependant disease may be unresponsive to ACTH.  

'''Low dose dexamethasone test''': Will reliably differentiate between normal and hyperadrenocorticism dogs. Sample before and 3 and 8 hours after i/v dexamethasone at 0.01mg/kg. Normal and dogs with pituitary dependant disase show suppression of cortisol production to &lt;50% at 3 hours whereas dogs with adrenal dependant disease have high cortisol levels which are not suppressed.  

'''Low dose dexamethasone test''': Will reliably differentiate between normal and hyperadrenocorticism dogs. Sample before and 3 and 8 hours after i/v dexamethasone at 0.01mg/kg (Bexfield and Lee, 2010). Normal dogs and dogs with pituitary dependant disease show suppression of cortisol production to <50% at 3 hours whereas dogs with adrenal dependant disease have high cortisol levels which are not suppressed.

'''High dose dexamethasone test''': Distinguishes pituitary and adrenal dependant disease once Cushings has been diagnosed. Dexamethasone dose is 0.1mg/kg. Pituitary dependant disease will show suppression of cortisol production due to negative feedback at the pituitary whereas adrenal dependant disease will not.

'''High dose dexamethasone test''': This test is used to distinguish pituitary and adrenal dependant disease in dogs once Cushings has been diagnosed and can help with diagnosis in cats. Dexamethasone dose is 0.1mg/kg (Bexfield and Lee, 2010). Pituitary dependant disease will show suppression of cortisol production due to negative feedback at the pituitary whereas adrenal dependant disease will not.

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Ultrasound of the adrenal glands can also be performed to distinguish if one is large or if both are bilaterally enlarged. This would distinguish from PDH (bilateral) and an adrenal tumour (one enlarged).  

Ultrasound of the adrenal glands can also be performed to distinguish if one is large or if both are bilaterally enlarged. This would distinguish from PDH (bilateral) and an adrenal tumour (one enlarged).  

== Treatment ==

== Treatment ==

'''Mitotane'''electively destroys the zona fasciculata and zona reticularis while sparing the zona glomerulosa. Mitotane will detroy the hyperplastic adrenal cortex  and the remaining tissue will then provide normal plasma cortisol concentrations. The animal will no longer be able to raise its plasma cortisol above around 20- 50 nmol/L, which will provide significant clinical improvement. You may need to use an induction dose for 5- 7 days follwed then by a maintenence dose of twice a week administration.  

'''Mitotane''' electively destroys the zona fasciculata and zona reticularis while sparing the zona glomerulosa. Mitotane will destroy the hyperplastic adrenal cortex  and the remaining tissue will then provide normal plasma cortisol concentrations. The animal will no longer be able to raise its plasma cortisol above around 20-50 nmol/L, which will provide significant clinical improvement. You may need to use an induction dose for 5-7 days followed by a maintenance dose of twice a week administration.  

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Animals that are treated with mitotane cannot mount a sufficient immune response in cases of stress, trauma or illness. As a consequence, from the onset of mitotane treatment, prednisolone should always be prescribed so that in these cases the owner can administer the prednisolone whilst awaiting veterinary assistance.

Animals that are treated with mitotane cannot mount a sufficient immune response in cases of stress, trauma or illness. As a consequence, from the onset of mitotane treatment, prednisolone should always be prescribed so that in these cases the owner can administer the prednisolone whilst awaiting veterinary assistance.

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'''L-Deprenyl'''is a monoamine oxidase inhibitor. Increases dopamine input to hypothalamus and pituitary and so inhibits ACTH secretion.  

'''L-Deprenyl''' is a monoamine oxidase inhibitor. Increases dopamine input to hypothalamus and pituitary and so inhibits ACTH secretion.  

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Pituitary tumours may be treated with ''radiotherapy'' or ''surgery''. A bilateral adrenalectomy can be performed in some cases. Hypophysectomy has been performed in some countries with good success rates. This involves removal of the gland through the nose and must be performed in a specialist referral centre.

Pituitary tumours may be treated with ''radiotherapy'' or ''surgery''. A bilateral adrenalectomy can be performed in some cases. Hypophysectomy has been performed in some countries with good success rates. This involves removal of the gland through the nose and must be performed in a specialist referral centre.

 

 

== References ==

== References ==

Blood, D.C. and Studdert, V. P. (1999) Saunders Comprehensive Veterinary Dictionary (2nd Edition), Elsevier Science.

 

Bexfield, N. and Lee, K. (2010)''' BSAVA Guide to Procedures in Small Animal Practice''', ''British Small Animal Veterinary Association

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Church, D (2008) Endocrine System Stugy Guide, Royal Veterinary College.

Blood, D.C. and Studdert, V. P. (1999) '''Saunders Comprehensive Veterinary Dictionary''' (2nd Edition),'' Elsevier Science''.

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Ettinger, S.J. and Feldman, E. C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition), W.B. Saunders Company.

Church, D (2008)''' Endocrine System Stugy Guide, '''''Royal Veterinary College.''

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Ettinger, S.J, Feldman, E.C. (2005) Textbook of Veterinary Internal Medicine (6th edition, volume 2), W.B. Saunders Company.

Ettinger, S.J. and Feldman, E. C. (2000)''' Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2''' (Fifth Edition),'' W.B. Saunders Company.''

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Fossum, T. W. et. al. (2007) Small Animal Surgery (Third Edition), Mosby Elsevier.

Ettinger, S.J, Feldman, E.C. (2005)''' Textbook of Veterinary Internal Medicine '''(6th edition, volume 2),'' W.B. Saunders Company''.

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Foster, A, and Foll, C. (2003) BSAVA small animal dermatology (second edition), British Small Animal Veterinary Association.

Fossum, T. W. et. al. (2007) '''Small Animal Surgery''' (Third Edition), ''Mosby Elsevier.''

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Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial.

Foster, A, and Foll, C. (2003)''' BSAVA small animal dermatology '''(second edition), ''British Small Animal Veterinary Association.''

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Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition), Mosby Elsevier.  

Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine '''(Fourth Edition),'' Mosby Elsevier. ''

[[Category:Bones_-_Metabolic_Pathology]] [[Category:To_Do_-_Review]] [[Category:Neurological_Diseases_-_Dog]] [[Category:Endocrine_Diseases_-_Dog]] [[Category:Adrenal_Glands_-_Pathology]]

[[Category:Bones_-_Metabolic_Pathology]] [[Category:Expert_Review - Small Animal]] [[Category:Neurological_Diseases_-_Dog]] [[Category:Endocrine_Diseases_-_Dog]] [[Category:Adrenal_Glands_-_Pathology]]