Hypoadrenocorticism

Question 1

Actions of glucocorticoids

Answer 1

Part of the fight or flight response
A ‘stress’ hormone
Counteracts the effects of stress
Essential for life!

Question 2

Aldosterone regulation

Answer 2

Renin-angiotensin system
- decreased blood pressure (baroreceptors in wall of afferent arteriole, and cardiac and arterial) -> renin release -> angiotensin release -> aldosterone release

Potassium concentration
- Very small increases -> aldosterone release

Question 3

Function of aldosterone

Answer 3

Regulation of BP
Acts on cells of diatal tubule and collecting duct to increase reabsorption of Na, Cl and water
Stimulates secretion K+ into tubular lumen
Stimulates secretion of H+ in exchange for K+ in the collecting tubules, so regulating acid/base

Question 4

Aetiology of hypoadrenocorticism

Answer 4

1. Primary hypoadrenocorticism - Addison’s
2. secondary hypoadrenocorticism - deficiency of ACTH
3. Iatrogenic hypoadrenocorticism

Question 5

Primary hypoadrenocorticism (Addisons)

Answer 5

Deficiency of glucocorticoids (cortisol) and mineralocorticoids (aldosterone).

Occurs with loss of 85-90%

Signalment: young/middle aged, female dogs. Very rare in cats.

Question 6

Causes of Primary hypoadrenocorticism (Addisons)

Answer 6

Idiopathic atrophy - probably immune mediated destruction

Iatrogenic - drugs (mitotane, trilostane), surgery (bilateral adrenalectomy

Question 7

Pathophysiology of Primary hypoadrenocorticism (Addisons)

Answer 7

Aldosterone deficiency
- loss of Na+, Cl, H2O
- retention of K+, H+
- Pre-renal failure

Glucocorticoid
- decreased stress tolerance
- GI signs
- Weakness
- appetite loss
- anaemia
- imparied gluconeogenesis

Question 8

Seconday hypoadrenocorticism

Answer 8

Deficiency of ACTH
Only cortisol deficient as RAS system still stimulating aldosterone
Rare

Question 9

Iatrogenic hypoadrenocorticism

Answer 9

Exogenous steroids -> adrenal atrophy

Cortisol deficiency only

Patient may have signs of Cushing’s syndrome: PU/PD, alopecia, pot belly, hepatomegaly

May develop signs of Addisons if steroids abruptly discontinued

Question 10

Clinical signs of a chronic presentation of hypoadrenocorticism

Answer 10

Worsened by stress
Waxing and waning signs

Anorexia
Vomiting
Lethargy
Depression
Weakness
Shivering
Weight loss
PU/PD
Abdominal pain
GI haemorrhage

Question 11

Acute presentation of Addisonian crisis

Answer 11

Medical emergency, can be fatal

Hypovolaemic shock, with paradoxical relative bradycardia

Collapsed or extremely weak
Hypothermic
History of V+/D+
Abdominal pain
Cardiac abnormalities
Depression
Thin
Weak
Dehydration
Bradycardia
Melena

Question 12

Blood parameter changes in hypoadrenocorticism

Answer 12

Reflect lack of aldosterone and cortisol, and hypovolaemia

Question 13

What does lack of aldosterone cause?

Answer 13

Renal loss of water, sodium, and chloride.
Retention of potassium and hydrogen ions.
Pre-renal failure

Question 14

What does glucocorticoid deficiency cause?

Answer 14

Decreased stress tolerance, appetite loss, impaired gluconeogenesis, normocytic normochromic anaemia.

Question 15

Biochemistry findings in hypoadrenocorticism

Answer 15

Hyperkalaemia
Hyponatraemia
Hypochloridaemia
Decreased Na:K ratio

10% do not have classic electrolyte findings

Azotaemia (increased renal parameters)
Hypercalcaemia
Hypoglycaemia

Question 16

Haematology findings in hypoadrenocorticism

Answer 16

Lack of stress leukogram
Lymphocytosis
Eosinophilia
Neutropaenia
Anaemia

Question 17

Urinalysis findings in hypoadrenocorticism

Answer 17

May be high USG due to dehydration and azotaemia

BUT chronic sodium wasting can reduce urine concentrating - medullary washout

Question 18

ECG changes in hypoadrenocorticism

Answer 18

Result of the level of hyperkalaemia

> 5.5mmol/l: T wave peaking and Q-T shortening

> 6.5mmol/l: increased QRS duration

> 7.0 mmol/l: P wave decreased, P-R interval prolonged

> 8.5mmol/l: P waves absent and severe bradycardia

Question 19

Radiographic changes of hypoadrenocorticism

Answer 19

Usually relate to hypovolaemia e.g. microcardia, decreased pulmonary vessel size, reduced caudal vena cava, microhepatica.

Occasionally oesophageal dilation can be seen due to muscle weakness

Question 20

Features likely to make you suspicious of hypoadrenocorticism

Answer 20

Electrolyte abnormalities (Na+:K+ ratio <23) - but not always abnormal

Lack of stress leukogram in a sick dog

Young dog with a history of chronic illness

Question 21

Diagnostic tests for hypoadrenocorticism

Answer 21

Basal cortisol
ACTH stimulation
Aldosterone pre and post ACTH
Endogenous ACTH

Question 22

Basal cortisol in the diagnosis of hypoadrenocorticism

Answer 22

A value >55nmol effectively rules out hypoadrenocorticism.

If lower ACTH stimulation test is needed.

Question 23

ACTH stimulation test in the diagnosis of hypoadrenocorticism

Answer 23

The most useful test
Can also be used to diagnose atypical hypoadrenocorticism
A dog with hypoadrenocorticism will show no or minimal response to ACTH stimulation

Question 24

Aldosterone pre and post ACTH in the diagnosis of hypoadrenocorticism

Answer 24

Used to distinguish primary and secondary causes.

If secondary, dog will have raised post ACTH aldosterone, if primary it will have no response.

Question 25

Endogenous ACTH in the diagnosis of hypoadrenocorticism

Answer 25

Will be high in primary disease and low if secondary or iatrogenic disease

Question 26

Treatment of an acute Addisonian crisis

Answer 26

1. Restore intravascular volume 2. Reversal of hyperkalaemia 3. Reversal of hyponatraemia 4. Provision of glucocorticoids and mineralocorticoids 5. (Correction of any life-threatening arrhythmias)

Question 27

Restoring intravascular volume in an Addisonian crisis

Answer 27

Using aggressive fluid therapy 0.9% NaCl or lactated Ringer's (Hartmann's) suitable 20-90 ml/kg/hr Assess effectiveness frequently Once volume restored reduce to maintenance rate Continue fluids until hydratio status, urine output, serum electrolytes, and azotaemia are corrected.

Question 28

Reversal of hyperkalaemia in an Addisonian crisis

Answer 28

Can be life-threatening due to negative effects on myocardial cells IV fluid therapy +++ 10% Calcium gluconate Sodium bicarbonate IV dextrose/glucose IV soluble insulin

Question 29

Reversal of hyponatraemia in an Addisonian crisis

Answer 29

Usually IV fluids are all thats needed

Question 30

Provision of glucocorticoids and mineralocorticoids in an Addisonian crisis

Answer 30

Acute period: IV administration of a rapid acting glucocorticoid - Dexamethasone (can be used alongside ACTH stimulation test) - Hydrocortisone - Methylprednisolone sodium - Prednisolone Long term: - Desoxycortone pivalate (mineralocorticoid replacement, no glucocorticoid activity so needs that too) - Fludrocortisone (mineralocorticoid and glucocorticoid replacement, oral medication, now very expensive)

Question 31

Monitoring hypoadrenocorticism therapy

Answer 31

Do not repeat the ACTH stim test! Clinical signs and electrolytes

Question 32

Prognosis of Addisonian crisis therapy

Answer 32

Good, providing the dog survives the acute event Median survival time of 2.5 to 5.5 years following doagnosis