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Hyperadrenocorticism is common in older dogs and it causes a wide range of
clinical signs including a pot-bellied appearance and hairloss, with an
increase in thirst and urination. It is rare in cats but when it occurs it is
often associated with over diabetes mellitus..
naturally occurring disease is caused by excess
production of a hormone, cortisol, by the adrenal gland. Cortisol is produced by
cells located in the outer cortex region of the adrenal gland and overproduction
may be due to :
- Disease of the adrenal gland itself - usually a tumour in one of the
adrenal glands (may be a benign adenoma, or a malignant carcinoma).
Accounts for about 10-15%of all cases in dogs.
- Disease of the pituitary gland in the brain- usually a small (less than
1 cm diameter) benign neoplasm (adenoma)- resulting in increased secretion
of the hormone adrenocorticotrophic hormone (ACTH) which causes bilateral
hyperplasia of the adrenal glands, and increased cortisol secretion.
So-called pituitary-dependent hyperadrenocorticism accounts for over 85%
of all reported cases in dogs and most cases in cats.
- Rarely there is a failure of feedback mechanisms to the brain to reduce
ACTH production. The precise cause of this is not known.
Hyperadrenocorticism is also seen as a clinically-induced problem :
- Iatrogenic hyperadrenocorticism is due to the direct effect of prolonged
treatment with high doses of corticosteroid drugs. These drugs are widely
used in veterinary medicine for the management of a variety of conditions.
In this case the adrenal glands atrophy, and hypoadrenocorticism (Addison's
Disease) can occur if drug administration is stopped.
Cushings disease is most commonly seen in Boxers, Dachshunds, Lhasa Apso,
Poodles (Miniature and Toy) and small Terrier breeds including Jack Russells and
Staffordshire Bull Terriers..
It usually occurs in dogs over 4 years of age, and is particularly common in
dogs over 8 years of age, and adrenal-dependent hyperadrenocorticism occurs in
older animals - usually over 10 years of age.
For pituitary dependent Cushings disease slightly more females are affected
than males, but for adrenal tumours females are almost three times as likely to
Signsommon clinical signs of hyperadrenocorticism include :
- Pot-bellied appearance - due to increased fat deposition, weakness of
the abdominal muscles, and an enlarged liver
- Increased thirst - affected dogs drink over 100 ml/kg body weight/day.
This is secondary to increased urine losses, and due to a direct effect of
glucocorticoids on the thirst centre in the brain. In cats polydipsia is a
late sign associated with hyperglycaemia and overt diabetes.
- Increased urine loss - passes over 50ml/kg body weight/day . Due to
affects of glucocorticoids on antidiuretic hormone. In cats polyuria is a
late sign associated with glycosuria and over diabetes.
- Increased appetite - direct affect of corticosteroids on the brain
- Hair loss - bilaterally symmetrical - particularly along the back,
ventral abdomen and the flanks. It is not itchy and is caused by the
effect of corticosteroids which inhibit the anagen phase of hair growth.
- Thinning of the skin
- Large macules (circular pigmented areas) form on the skin
- Calcium deposits in the skin (called calcinosis cutis)
- Generalised muscle weakness - sometimes with obvious muscle wastage (eg
temporal muscles) - due to increased protein catabolism caused by the high
concentrations of corticosteroids.
- Abnormal muscle contractions and rigidity (called myotonia) is sometimes
present, creating a stiff gait when walking.
- Lethargy and poor exercise tolerance - often mistaken for normal
- Panting at rest
- Sometimes behaviour changes - urinating in the house at night due to
increased urine production; pacing, head pressing ...neurological signs
due to the presence of a large (over 1 cm diameter) brain tumour
- Sometimes apparent blindness due to pressure from a large brain tumour
- Siezures due to secondary spread of a brain tumour (uncommon)
- Atrophy of the testicles occurs in males, and there is inhibition of the
oestrus cycle in bitches. These effects are both due to the enhanced
feedback mechanism of high cortisol concentrations on the pituitary which
inhibits the secretion of gonadotrophic hormones from the pituitary.
ComplicationsHyperadrenocorticism may occur in conjunction with other endocrine disorders
such as diabetes mellitus (c10% of canine cases)
laboratory findings in hyperadrenocorticism include :
- Blood biochemistry
- Greatly increased alkaline
phosphatase concentrations - glucocorticoid isoenzyme. This is rarely
noticed in cats as they can clear alkaline phosphatase rapidly.
- Increased Alanine
aminotransferase (ALT) concentrations - liver damage due glycogen
- Increased blood glucose -
insulin resistance due corticosteroids. In cats hyperglycaemia is a
- Increased cholesterol and lipid
concentrations - corticosteroid stimulation of lipolysis
- Bromsulphthalein retention -
increased due to liver damage
- Bile acids - increased
- Low blood urea and creatinine
concentrations - due to diuresis
- Low lymphocyte and eosinophil
- Increased neutrophil, monocyte
and erythrocyte counts
- T4 (thyroxine) concentrations
are low in 70% of canine cases of hyperadrenocorticism. Due negative
feedback of cortisol on the secretion of Thyrotropin-releasing hormone
from the pituitary gland, and possibly increased rate of metabolic
- Urine test
- Specific gravity less than 1.010
in dogs. They can concentrate urine if deprived of water.
- Glycosuria - present in 10% with
diabetes mellitus. It is common in cats.
- 50% of cases of canine
hyperadrenocorticism have a urinary tract infection
Specific laboratory tests :
1. Elevated basal plasma cortisol concentrations:
- Above 330 nmol/l - highly suggestive
- Above 410 nmol/l - definite
2. ACTH Stimulation test
2 hours post-ACTH administration (0.25mg tetracosactrin intramuscularly)
collect 5ml blood in heparin -
- Plasma cortisol concentrations over 550nmol/l indicate
- 470 nmol/l - 550 nmol/l = borderline - repeat in 3 months
- Less than 470 nmol/l - suggest negative but a few pituitary-dependent
and almost 50% adrenal-dependent hyperadrenocorticism cases have values
below this !
3. Low dose dexamethasone suppression test (most
8 hours after administration of 0.01mg dexamethasone / kg body weight collect
- Less than 40 nmol/l cortisol - normal
- Greater than 40 nmol/l cortisol - hyperadrenocorticism*
(* prior treatment with anticonvulsive therapy, glucocorticoids and some
clinical cases do not show suppression )
4. High dose dexamethasone suppression test
Collect blood pre-dexamethasone treatment and at 3 and 8 hours
post-administration of 0.1mg dexamethasone / kg bdy weight :
- If plasma cortisol concentrations are less than 50% of the basal
concentration after 3 or 8 hours pituitary-dependent hyperadrenocorticism is
- If following both tests plasma concentrations are greater than 50%
of the basal concentration adrenal neoplasia is suggested, although 15% of
pituitary-dependent cases may cause poor suppression with this test.
Thus far treatments except for adrenalectomy have not been very successful in
cats, whereas they have in dogs.
Treatment depends upon the primary cause :
- Iatrogenic hyperadrenocorticism
Gradually reduce the administered dose of corticosteroid therapy.
- Pituitary-dependent hyperadrenocorticism
(NB care is needed to avoid overdosage and
collapse due to hypoadrenocorticism. Manage such an incident with
injectable glucocorticoid treatment and stop mitotane treatment until polyuria
1. Mitotane (op'DDD) which destroys the adrenal
cortex is very successful :
- Method 1 50mg/kg body weight/day with food in the
evening for 10 days, then weekly doses for 2 weeks , then 25mg/kg/week
- Method 2 50mg/kg body weight/day. Measure daily water
intake. When water intake is less than 60ml/kg body weight/day , or one of
the following side-effects occur : the dog stops eating, develops
vomiting, diarrhoea, or depression, reduce the dose to a maintenance of
25mg/kg body weight/week
If the side-effects become severe a small amount of cortisol can be
administered by mouth.(1.5mg/kg body weight per day for up to 2 weeks), or
prednisolone at 2mg/kg body weight can be given for 2 days then gradually
If there is no response to mitotane the most likely cause is adrenal
neoplasia or misdiagnosis. Occasionally much higher doses of mitotane are needed
in some individuals If dogs have a relapse after stabilisation
repeat ACTH stimulation tests should be performed.
2. Ketoconazole - inhibits glucocorticoid synthesis, reduces
circulating cortisol concentrations and reduces the response to ACTH. Dose
5mg/kg body weight/ twice daily for 7 days then 10mg/kg body weight/ twice
daily, An ACTH stimulation test should be performed after 10 days on 10mg/kg
body weight twice daily and the dose can be increased to15mg/kg twice daily if the cortisol concentration
is greater than 300 nmol/l following the ACTH stimulation test. However, it is expensive and can cause
hepatotoxicity, as well as anorexia, vomiting and diarrhoea .
3. Trilostane (Vetoryl - Dechra is a licensed veterinary product
for use in dogs. It does not cure Cushing's syndrome but it reduces production
of cortisol by the adrenals and so can help control the disease.
This procedure (called hypophysectomy) is technically difficult although the
reported success rate (45%) is good.
Has been used successfully to treat large pituitary tumours. CT or MRI
imaging are needed pre-operatively to plan the radiation dose.
- Adrenal-dependent hyperadrenocorticism
Adrenalectomy is the treatment of choice for unilateral adrenal
tumours provided there is no evidence of metastatic spread to vital organs
such as the lungs. The affected gland is usually much larger than the other
(which has atrophied), and the affected gland may appear to be calcified on
Post-operatively both mineralocorticoids and glucocorticoids must be given
until the atrophied gland has returned to normal function. Wound healing is
poor in dogs with hyperadrenocorticism.
Mitotane - see above
Ketoconazole - may be used in older dogs, but it is potentially
hepatotoxic. Dose 30mg/kg body weight/day.
The success of treatment is monitored by a return to normal appetite,
drinking and urination and regrowth of hair. The success of treatment can be
remarkable in some cases. By 8 weeks after the start of treatment significant
improvement should be recognised.
It is reported that about 80% of pituitary-dependent cases respond well, though
neurological signs will occur in some cases later as the tumour gets bigger.
Life-expectancy following diagnosis and treatment is over 2 years with many
patients surviving over 7 years.
Long term problems
should be re-examined every 6 months as relapses and transient overdoses do
occur. Some individuals develop resistance to the mitotane.
be Updated November 2013