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== [[Image:Cushings alopecia.jpg|thumb|right|200px|<small><center><b>Cushings Alopecia</b>. Courtesy of A. Jefferies</center></small>]]&nbsp;Synonyms ==

Cushings Disease

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

 

== Introduction ==

== Introduction ==

 

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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'''Pituitary Dependant Hyperadrenocorticism [[Image:Chromophobe adenoma.jpg|thumb|right|150px|<small><center><b>Chromophobe Adenoma</b>. Courtesy of A. Jefferies</center></small>]] [[Image:Nodular hyperplasia.jpg|thumb|center|150px|<small><center><b>Adrenal Nodular Hyperplasia</b>. Courtesy of A. Jefferies</center></small>]]

===Pituitary Dependant Hyperadrenocorticism ===

 

80-85% cases of Cushings disease show bilateral adrenal hyperplasia due to excess stimulation by adrenocorticotrophic hormone (ACTH). There is a failure of the negative feedback mechanism at the level of the pituitary and so ACTH is produced in an unregulated fashion. This is thought to occur due to a functional chromophobe cell (Produces ACTH and MSH) neoplasia, although visible macroadenomas are only found in 10-15% cases with this aetiology. Most cases are therefore thought to be microadenomas and may be visualised by histopathological staining of the pituitary.  

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.  

'''Iatrogenic Hyperadrenocorticism'''

 

 

===Iatrogenic Hyperadrenocorticism===

 

This is created by the administration of parenteral corticosteroids.In these cases adrenal atrophy is induced as the administered steroids have a negative feedback effect on the pituitary and normal ACTH release is inhibited.  

This is created by the administration of parenteral corticosteroids.In these cases adrenal atrophy is induced as the administered steroids have a negative feedback effect on the pituitary and normal ACTH release is inhibited.  

== Clinical Signs ==

== Clinical Signs ==

Cortisol interferes with ADH action on the kidney resulting in '''polyuria and polydipsia'''. This, along with '''panting''' and '''lethargy''', are the most commonly seen clinical signs of hyperadrenocortiscm.

Cortisol interferes with antidiuretic hormone(ADH) action on the kidney resulting in '''polyuria and polydipsia'''. This, along with '''panting''' and '''lethargy''', are the most commonly seen clinical signs of hyperadrenocortiscm.

'''[[Liver - Anatomy & Physiology|Liver]]''': Cortisol induces enzymes to increase gluconeogenesis leading to '''hyperglycaemia''' in Cushings patients. The [[Pancreas - Anatomy & Physiology|pancreas]] attempts to maintain normal blood glucose by producing increasing amount of insulin. Eventually the [[Pancreas - Anatomy & Physiology|pancreas]] is exhausted inducing a diabetic state. Clinical signs will include hepatomegaly and abdominal enlargement, which may take the appearance of overall obesity.

'''[[Liver - Anatomy & Physiology|Liver]]''': Cortisol induces enzymes to increase gluconeogenesis leading to '''hyperglycaemia''' in Cushings patients. The [[Pancreas - Anatomy & Physiology|pancreas]] attempts to maintain normal blood glucose by producing increasing amount of insulin. Eventually the [[Pancreas - Anatomy & Physiology|pancreas]] is exhausted inducing a diabetic state. Clinical signs will include hepatomegaly and abdominal enlargement, which may take the appearance of overall obesity.

Cortisol stimulates protein catabolism for gluconeogenesis so patients exhibit '''muscle weakness'''. Protein catabolism and weakness gives '''poor wound healing'''. Collagen damage due to protein catabolism allows the deposition of calcium in the skin. Calcium acts as a foreign body producing a ''granulomatous reaction''. This is called Calcinosis Cutis.  

Cortisol stimulates protein catabolism for gluconeogenesis so patients exhibit '''muscle weakness'''. Protein catabolism and weakness gives '''poor wound healing'''. Collagen damage due to protein catabolism allows the deposition of calcium in the skin. Calcium acts as a foreign body producing a ''granulomatous reaction''. This is called Calcinosis Cutis.  

MSH production stimulates the pigmentation of the skin with melanin. Cortisol inhibits the growth phase of the hair cycle (ANAGEN) so hair growth stops. When epilated over areas of high friction there will be '''bilaterally symmetric non-pruritic alopecia'''.

MSH production stimulates the pigmentation of the skin with melanin. Cortisol inhibits the growth phase of the hair cycle (ANAGEN) so hair growth stops. When epilated over areas of high friction there will be '''bilaterally symmetric non-pruritic alopecia'''.

Lipolysis is stimulated by cortisol to provide precursors for gluconeogenesis. Seen clinically as a redistribution of fat to the abdomen and back of the neck; '''Pot-bellied appearance'''.  

Lipolysis is stimulated by cortisol to provide precursors for gluconeogenesis. Seen clinically as a redistribution of fat to the abdomen and back of the neck; '''pot-bellied appearance'''.  

'''Immune system''': Cortisol is '''anti-inflammatory''' by a number of mechanisms E.g. stabilising lysosomal membranes. The circulation will contain fewer lymphocytes and eosinophils.  

'''Immune system''': cortisol is '''anti-inflammatory''' by a number of mechanisms e.g. stabilising lysosomal membranes. The circulation will contain fewer lymphocytes and eosinophils.  

 

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 diagnositc 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 (&gt;600nmol/l).  

Adrenal dependant disease may be unresponsive to ACTH.  

Adrenal dependant disease may be unresponsive to ACTH.  

== 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 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.