Hyperadrenocorticism Flashcards by Sophie Robinson

Give the medical term for Cushings disease

Hyperadrenocorticism

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Describe the two components of the adrenal gland

Cortex - synthesises and secretes steroid hormones
Medulla - synthesises and secretes catecholamines

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Which substances are produced in the adrenal cortex?

Mineralocorticoids
Glucocorticoids
Sex hormones and precursors

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Describe the production of glucocorticoids

Secreted by cells in the zona fasciculata under control of ACTH released from the anterior pituitary, itself controlled by CRF released by the hypothalamus.
Cortisol feeds back negatively on the anterior pituitary and the hypothalamus

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What is the role of cortisol?

Involved in homeostasis during stress

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List the functions of glucocorticoids

Gluconeogenesis
Glycogen synthesis
Immune/Inflammation suppression
Catabolism (fat and protein degradation)
Inhibition of DNA/protein synthesis

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Describe the production/secretion of mineralocorticoids

Secreted by cells of the zona glomerulosa under the influence of angiotension II (and to a lesser extent of ACTH).

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Name the main mineralocorticoid and its function

Aldosterone
Retention of sodium and excretion of potassium by the kidney

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What are the functions of catecholamines?

Catecholamines stimulate a variety of systems in preparation for fight/flight response thus, effects include increases in heart rate, blood pressure and blood glucose concentration

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How is hyperadrenocorticism (Cushings) classified?

Pituitary dependant or Adrenal dependant

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Describe pituitary dependant hyperadrenocorticism

Accounts for 80% of cases
It is caused by excessive secretion of ACTH by a pituitary tumour.
This leads to bilateral hyperplasia of the adrenal cortices and excessive cortisol secretion by the adrenal glands.
Most pituitary tumours are adenomas.

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Describe adrenal dependant hyperadrenocorticism

Caused by an adrenal tumour, which secretes
excessive amounts of cortisol.
This causes a decrease in ACTH secretion by the pituitary gland and atrophy of the uninvolved adrenal gland.
About 50% of adrenal tumours are adenomas and 50% are adenocarcinomas.

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What is the cause of iatrogenic hyperadrenocorticism?

Excessive glucocorticoid administration

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Describe the predisposing factors for cushings

Middle aged/older dogs
No sex
Breeds - Poodles, Terriers, Dachshunds, Beagles and Labradors appear to be overrepresented
Rare in cats - but some association with insulin resistant diabetes mellitus
PDH: more common in small breeds
ADH: more common in large breeds

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List the common clinical signs of Hyperadrenocorticism

Polydipsia
Polyuria
Polyphagia
Panting
Abdominal distention
Endocrine alopecia
Hepatomegaly
Muscle weakness
Systemic hypertension

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List the less common clinical signs of Hyperadrenocorticism

Lethargy
Hyperpigmentation
Comedones
Thin skin
Poor hair regrowth
Urine leakage
Insulin-resistant DM

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List the uncommon clinical signs of Hyperadrenocorticism

Thromboembolism
Ligament rupture
Facial nerve palsy
Pseudomyotonia
Testicular atrophy
Persistent anoestrus

Why do animals with Hyperadrenocorticism present with a ‘pot belly’?

This occurs due to weakness of the abdominal muscles
and hepatomegaly - also has thin skin and prominent veins in this region

Where is muscle atrophy most visible in hyperadrenocorticm cases?

Temporal region
Hindlimbs

What is calcinosis cutis?

Large plaques on the skin that can ulcerate and become secondarily infected.

Describe the coat changes seen in hyperadrenocorticism, why do these occur?

Thinning of the hair leading to bilaterally symmetrical alopecia often affecting the ventral abdomen, flanks and neck.
This is because of the inhibitory effect of cortisol on the growth phase of the hair cycle.

Describe the haematology changes seen in hyperadrenocorticism

Neutrophilic leukocytosis
Lymphopenia
Eosinopenia
Thrombocytosis
Mild erythrocytosis

Describe the serum biochemistry changes seen in hyperadrenocorticism

Increased ALKP
Increased ALT - usually mild
Hypercholesterolaemia - raised cholesterol due to lipolysis
Hypertriglyceridaemia
Hyperglycaemia - gluconeogenic effect of steroids

Describe the urinalysis changes seen in hyperadrenocorticism

Specific gravity ≤1.018–1.020
Proteinuria
Urinary tract infection

Why is a low USG seen in hyperadrenocorticism

Most animals with HAC have isosthenuric or even hyposthenuric urine. Glucocorticoids antagonise the effect of ADH in the renal tubules, reducing the urine concentration ability

Why are urinary tract infections seen in hyperadrenocorticism

This occurs due to the immunosuppressive effect of steroids coupled with the low USG

Describe the ACTH stimulation test for Cushings - what are normal and abnormal results?

Cortisol levels are measured at 0 and 1 hour and the dog is given synthetic ACTH iv at 0 hours. A normal healthy animal should have post ACTH concentrations that are 2-3 times higher than the basal values. Abnormal results - post ACTH cortisol values will be much higher than normal

Describe the low dose dexamethasone test for Cushings - what are normal and abnormal results?

- Blood cortisol levels are assessed 0, 3 and 8 hours after administration of dexamethasone iv. - Normal animal = suppresses cortisol concentrations to <50% of the basal level after 3 hours and to <40 nmol/l after 8 hours. - An animal with adrenal dependent HAC will fail to suppress at 3 and 8 hours - Most animals with pituitary dependent HAC will suppress at 3 hours and escape suppression at 8 hours

Describe the purpose of the high dose dexamethasone test for Cushings

The protocol is the same as for the low dose but the dose of dexamethasone is increased. This test is used to differentiate adrenal dependent from pituitary dependent HAC once HAC has been confirmed by one of the above tests. It has been largely superseded by the ACTH assay.

Describe the normal and abnormal results for the high dose dexamethasone suppression test

Most animals with pituitary dependent HAC (70-80%) will suppress to <50% of the basal value after 3 hours and to <40nmol/l after 8 hours. Animals with adrenal dependent HAC will fail to suppress

Which test is the most reliable for differentiating pituitary dependent HAC and adrenal dependant HAC?

ACTH assay

Describe how the ACTH assay differentiates pituitary dependent HAC and adrenal dependant HAC?

Dogs with PDH have high or normal ACTH concentrations Dogs with adrenal tumours have low ACTH concentrations.

How may radiography be used for hyperadrenocorticism diagnoses?

May show hepatomegaly and calcification Occasionally adrenal tumours seen

How can ultrasound be used for hyperadrenocorticism diagnoses?

This can be a useful way to differentiate PDH from adrenal tumours. Dogs with PDH usually have normal or bilaterally enlarged adrenal glands. Adrenal tumours are usually unilateral and can be seen on abdominal ultrasound

Which drugs is the only licensed drug for the treatment of hyperadrenocorticism?

Trilostane

How is trilostane treatment monitored?

Clinical Signs ACTH stimulation - Can be 10-14 days but if dogs well, 3 months - Repeat q 3months for ﬁrst year then q 6

What are the possible side effects of trilostane?

Adrenal necrosis Hypoadrenocorticism Lack of efﬁcacy Vomiting and Diarrhoea

Which drugs can be used when trilostane is not effective or contrainidcated?

Mitotane - need a license from the VDS to use it

How can you treat hypertension due to Cushings?

Benazepril

What is the treatment of choice for adrenal dependant hyperadrenocortisism?

Unilateral adrenalectomy

Describe the post-op support needed following an adrenalectomy

Post operative support with glucocorticoids is important as the uninvolved gland will have atrophied as a result of excessive cortisol secretion by the adrenal tumour

Describe the prognosis of hyperadrenocorticism

Untreated dogs die as a result of different complications like thromboembolic disease, secondary infections, hepatic and renal disease, etc. If appropriately treated and monitored, they can live for many months or years with a good quality of life. The best prognosis is for animals with adrenal adenomas that are successfully surgically removed. Dogs with adrenal carcinomas can live for months or years after surgery