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===Pathophysiology===
===Pathophysiology===
The glucococorticoid hormone '''cortisol''' enables animals to cope with stress while the minerlaocorticoid '''aldosterone''' plays a critical role in the regulation of sodium and potassium concentrations and of extracellular fluid volume. Aldosterone normally acts to increase sodium reabsorption and potassium excretion in the kidney so deficient aldosterone secretion will result in '''hyponatraemia''', '''hypochloraemia''' and '''hyperkalaemia'''.
The glucococorticoid hormone '''cortisol''' enables animals to cope with stress while the minerlaocorticoid '''aldosterone''' plays a critical role in the regulation of sodium and potassium concentrations and of extracellular fluid volume. Aldosterone normally acts to increase sodium reabsorption and potassium excretion in the kidney so deficient aldosterone secretion will result in '''hyponatraemia''', '''hypochloraemia''' and '''hyperkalaemia'''. Since they are unable to regulate their body sodium concentration, Addisonian animals become severely dehydrated and hypovolaemic, reducing the perfusion of peripheral tissues. During an Addisonian crisis, this can result in gastro-intestinal haemorrhage and allow translocation of bacteria across the gut barrier.
Deficiency of cortisol results in '''hypoglycaemia''' (as cortisol usually antagonises the action of insulin), increased circulating levels of [[Lymphocytosis|lymphocytes]] and [[Eosinophilia|eosinophils]] and increased skin pigmentation. This latter syndrome occurs as low levels of glucocorticoids allow increased ACTH production as negative feedback on the pituitary is removed or decreased. As ACTH is released, so is MSH (Melanocyte Stimulating Hormone), increasing the pigmentation of the skin in chronic cases of hypoadrenocorticism.
Deficiency of cortisol results in '''hypoglycaemia''' (as cortisol usually antagonises the action of insulin), increased circulating levels of [[Lymphocytosis|lymphocytes]] and [[Eosinophilia|eosinophils]] and increased skin pigmentation. This latter syndrome occurs as low levels of glucocorticoids allow increased ACTH production as negative feedback on the pituitary is removed or decreased. As ACTH is released, so is MSH (Melanocyte Stimulating Hormone), increasing the pigmentation of the skin in chronic cases of hypoadrenocorticism.
==Diagnosis==
==Diagnosis==
===Clinical Signs===
===Clinical Signs===
Addison's disease may present acutely as an '''Addisonian crisis''' or it may cause chronic disease over several months before it is diagnosed. Acutely, affected animals present in hypovolaemic [[Shock|shock]] with severe dehydration and bradycardia (caused by hyperkalaemia). This feature of the crisis is extremely suggestive of Addison's disease as hypovolaemic animals would usually be expected to be tachycardic.
Addison's disease may present acutely as an '''Addisonian crisis''' or it may cause chronic disease over several months before it is diagnosed. Acutely, affected animals present in '''hypovolaemic [[Shock|shock''']] with severe '''dehydration''' and '''bradycardia''' (caused by hyperkalaemia). This feature of the crisis is extremely suggestive of Addison's disease as hypovolaemic animals would usually be expected to be tachycardic. As with any cause of hypovolaemia, the peripheral pulse is often weak, the capillary refill time is prolonged and the heart sounds may not be clearly audible on auscultation.
Addisonian animals may suffer [[Control of Feeding - Anatomy & Physiology#The Vomit Reflex|vomiting]] acutely or chronically
Addisonian animals may suffer [[Control of Feeding - Anatomy & Physiology#The Vomit Reflex|'''vomiting''']] as part of an acute crisis or as a chronic intermittent syndrome. In the chronic form of the disease, animals are frequently '''anorexic''' and '''weak'''.
===Laboratory Tests===
===Laboratory Tests===
*'''Haematology''':
Complete analysis of blood samples is indicated for animals presenting acutely and for those that have a history of chronic intermittent vomiting and anorexia. The following changes may be documented:
*'''Haemoconcentration''' in an acute crisis due to rapid dehydration.
**Non-regenerative anaemia in chronic form; glucocorticoid deficiency decreases erythropoeisis.
*'''Non-regenerative anaemia''' in chronic form as glucocorticoid deficiency decreases erythropoeisis. Since it is possible for animals to undergo an acute crisis after suffering from hypoadrenocorticism for several weeks, any anaemia may be masked by the haemoconcentration that occurs due to hypovolaemia.
*'''Electrolyte imbalance''': as above.
*'''Electrolyte imbalances''' occur in 90% of patients, typically '''hyperkalaemia''', '''hyponatraemia''' and '''hypochloraemia'''. The sodium: potassium ratio of a normal animal is >27: 1 but this falls to <25: 1 in Addisonian animals.
*'''Pre-renal azotaemia''': elevated urea and creatinine.
*'''Pre-renal [[Azotaemia|azotaemia]]''' is common as hypovolaemic animals are unable to maintain adequate renal perfusion.
*'''Hypoglycaemia''' is a common finding in animals presenting in Addisonian crisis.
*'''[[Eosinophilia]]''' and '''[[Lymphocytosis|lymphocytosis]]''' occur due to the deficiency in glucocorticoids. In such a severely ill animal, a stress leucogram would usually be expected so this pattern is highly suggestive of hypoadrenocorticism. An elevated blood [[Urea|urea]] concentration may also occur due to gastro-intestinal haemorrhage which is a common finding in animals with Addison's disease.
===Other Tests===
===Other Tests===
Additional tests are available to confirm the diagnosis and assess the need for further supportive treatment. An '''ACTH stimulation test''' should be performed as soon as possible in animals presenting acutely. The pre-stimulation sample can be taken immediately, the ACTH (tetracosactin) is administered and the post- sample is collected after 1.5-2 hours. Although the results of the test may not be available for 24-48 hours, it is very useful to confirm the diagnosis when acute renal failure is considered to be a major differential diagnosis. A positive result is recorded if the level of cortisol is initially low and if this fails to respond to the injection of ACTH.
Since hyperkalaemia has significant effects on the membrane potential of excitable tissues, it is useful to perform an electrocardiogram ('''ECG''') to assess the function of the heart. Findings consistent with hyperkalaemia include small or absent P waves (indicating sino-atrial standstill), wide and small QRS complexes, short Q-T intervals, peaked T waves and long P-R intervals.
===Diagnostic Imaging===
===Diagnostic Imaging===
'''Plain radiographs''' of the chest and abdomen may show signs of hypovolaemia, including '''microcardia''', '''pulmonary underperfusion''' and '''microhepatica'''. Animals with Addison's disease may also develop [[Megaoesophagus|megaoesophagus]] due to muscle weakness. Ultrasound scans of the adrenal glands may be indicated to detect any evident pathological process that may account for the hypoadrenocorticism.
==Treatment==
==Treatment==
===Stabilisation===
Since collpased, bradycardic animals are unlikely to survive for long, urgent intervention is required to stabilise these patients. '''Intra-venous 0.9% sodium chloride (saline) solution''' should be provided at shock rates to restore normovolaemia and begin to correct the electrolyte imbalances. Additional '''glucose''' can be added to fluids in hypoglycaemic animals but blood glucose levels should be monitored closely if this is undertaken.
When the diagnosis has been made with some certainty, '''intra-venous glucocorticoid replacement therapy''' can be initiated together with a '''mineralocorticoid'''. Dexamethasone is the corticosteroid of choice as it has greater mineralocorticoid activity than other products. Although there is an intra-muscular injectable mineralocorticoid (desoxycorticosterone acetate) available in the USA, this is not usually required for stabilisation.
[[Gastroprotective Drugs|'''Gastro-protectant drugs''']] (such as sucralfate, ranitidine or omeprazole) may be administered to vomiting animals and '''antibiotics''' should be provided to any animals that develop pyrexia.
===Management===
In the long term, animals with Addison's disease require only a mineralocorticoid on a daily basis with intermittent courses of glucocorticoids during times of stress. The mineralocorticoid '''fludrocortisone acetate''' is available in an oral preparation and this is used most commonly for management.
During times of '''stress''', courses of corticosteroids (e.g. prednisolone) should be provided and '''table salt''' should be added to the diet. Water should be avaiable at all time and blood electrolyte levels should be monitored at regular intervals to ensure that the correct dose of fludrocortisone is used.
==Prognosis==
The prognosis for long term survival is excellent for animals with hypoadrenocorticism provided that any crisis is controlled.
[[Category:Cell Mediated Autoimmune Diseases]][[Category:To Do - James]]
[[Category:Cell Mediated Autoimmune Diseases]][[Category:To Do - James]][[Category:Dog]]