Canine hypoadrenocorticism

Question 1

Describe the anatomy of the adrenal cortex?

Answer 1

From outside to the inside:

• Zona glomerulosa (25% of cortex)
• Zona fasciculata (60% of cortex)
• Zona reticularis (15% of cortex)

Outer layer and inner layer tend to be effected by addisons disease.

Question 2

Draw a flow diagram detailing glucocorticoid release and it’s feedback mechanisms?

Answer 2

Question 3

Describe the actions glucocorticoids?

Answer 3

• Part of the “fight or flight” response
• A “stress” hormone
• Counteracts the effects of stress
• Essential for life!

Question 4

Describe aldosterone regulation?

Answer 4

Renin – angiotensin system

• blood pressure → renin release
• → angiotensin release
• → aldosterone release

Potassium concentration

• very small increases → aldosterone release

Renin release stimulated by:

• Baroreceptors in the wall of the afferent arteriole
• Cells of the macula densa in the early distal tubule which are stimulated by a reduction in Cl delivery
• Cardiac and arterial baroreceptors

Question 5

What is the function of aldosterone?

Answer 5

• Plays a central role in the regulation of BP
• Acts on cells of distal tubule and collecting duct to increase reabsorption of Na, Cl and hence water so increased BP
• Stimulates the secretion of K+ into the tubular lumen
• Stimulates secretion of H+ in exchange for K+ in the collecting tubules, so regulating acid/base
• It plays a central role in the regulation of blood pressure mainly by acting on the distal tubules and collecting ducts of the nephron, increasing reabsorption of ions and water in the kidney, to cause the conservation of sodium, secretion of potassium, increase in water retention, and increase in blood pressure and blood volume.
• Water follows Na

Question 6

What is primary hypoadrenocorticism and what is it also known as?

Answer 6

• Addison’s disease
• Deficiency of glucocorticoids (cortisol) and deficiency of mineralocorticoids (aldosterone)
• Occurs with loss of 85-90% of adrenal cortex
• ACTH tends to be high as the pituitary is screaming at the adrenals to do something and they arent responding

Question 7

What are some of the causes of primary hypoadrenocorticism in canines?

Answer 7

Idiopathic atrophy

• probably immune-mediated destruction
• associated with other endocrinopathies

Iatrogenic

• drugs: mitotane, trilostane
• surgery: bilateral adrenalectomy

Question 8

What is Secondary Hypoadrenocorticism?

Answer 8

• Pituitary stops producing ACTH
• Deficiency of ACTH
• Usually only cortisol deficient (electrolytes normal)
• Rare

Question 9

What is Iatrogenic hypoadrenocorticism?

Answer 9

• Exogenous steroids → adrenal atrophy
• oral, injectable, dermatological, otic or ophthalmic preparations
• Cortisol deficiency only
• Glucocorticoids can supress intrinsic adrenal activity. So be careful to taper of steroid drugs.
• Patient may have signs of Cushing’s syndrome whilst on steroids:
  
  • PU/PD, alopecia, pot belly, hepatomegally
  • Patient may develop signs of Addison’s disease if steroids abruptly discontinued
  • Can be life-threatening

Question 10

What is the signalment of canine hypoadrenocorticism?

Answer 10

• Young-middle aged dogs. Median age 4-6 years
• 70% females
• Any breed, but certain breed predispositions
• (Extremely rare in cats)

Question 11

Breeds with an increased risk of hypoadrenocorticism include:

Answer 11

• Standard poodles
• Bearded collies
• Great Dane
• Rottweiler
• WHWT
• Soft coated wheaten terrier
• Nova Scotia Duck Tolling Retriever (can get a juvenille version of addisons disease, present 5months-1year of age with addisons)

Question 12

What does pathognomonic mean?

Answer 12

A term, often used in medicine, that means characteristic for a particular disease. A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doubt. Labelling a sign or symptom “pathognomonic” represents a marked intensification of a “diagnostic” sign or symptom.

Question 13

What is the pathophysiology of hypoadrenocorticism?

Answer 13

Aldosterone deficiency

• Loss of Na+, Cl, H20
• Retention of K+, H+
• Pre-renal azotaemia (apparent renal failure)

Glucocorticoid deficiency

• Decreased stress tolerance, gastrointestinal signs, weakness, appetite loss, anaemia, impaired gluconeogenesis

History and clinical signs:

• Chronic: waxing waning form with non-specific signs
• Acute: Addisonian “crisis” form with marked hypovolaemia and azotaemia, hypercalcaemic

Question 14

What are the clinical signs of chronic hypoadrenocorticism?

Answer 14

• Usually vague and non-specific waxing and waning signs worsened by stress
• Anorexia, vomiting, diarrhoea, weakness, lethargy, depression and weakness
• Shivering, weight loss, PUPD, abdominal pain
• Consider Dx in any animal with waxing/waning signs – especially intermittent GI disease

Question 15

What are the clinical signs of acute hypoadrenocorticism?

Answer 15

• Signs caused by hypovolaemic shock
• MAY have paradox of relative bradycardia (due to hyperkalaemia)
• Usually collapsed or extremely weak, hypothermic with recent Hx of V+/D+
• Abdominal pain, melena is sometimes a feature and the disease can resemble pancreatitis clinically
• Dehydrated bradycardic depressed dog think addisons

Question 16

In an acute addisonian crisis what are common presenting signs?

Answer 16

• Depression 87 %
• Thin 82 %
• Weakness 66 %
• Dehydration 41 %
• Bradycardia 22 %
• Melena/hematochezia 17 %

Question 17

What is the biochemical profile of hypoadrenocorticism?

Answer 17

Classic findings

• hyperkalemia (­K+)
• hyponatremia (¯Na+)
• hypochloridemia (¯Cl-)
• Na:K ratio <23
• Approx 90% will have one or more of these findings

Due to aldosterone deficiency

• A drop in renal tubular resorption of Na+ and Cl
• A drop in excretion of K+ (and H+) Acid base disturbances because acid not being released into tubule

Question 18

What does the CBC (complete blood count) look like in a canine with hypoadrenocorticism?

Answer 18

Lack of stress leucogram (reverse stress leukogram)

• Absence of a lymphopenia is a strong indication of addisons.

Anemia (34%-71%)

• erythrocytosis due to lack of cortisol
• GI blood loss

Eosinophilia (10%)

• due to lack of cortisol

Lymphocytosis (13%)

• due to lack of cortisol

Question 19

What is the biochemical profile and urinanalysis profile for hypoadrenocorticism?

Answer 19

• Azotemia (­increase in renal parameters) ~61%
• Drop in urine specific gravity ~90% fails to go up because not enough Na to create a concentration gradient
  
  • inappropriately low in dehydrated animal
  • Na+ in urine filtrate impairs ability to retain water → medullary washout
• Hypercalcemia ~30%
• Hypoglycemia ~ 27 %
• Hyopcholseriama

Question 20

Define azotaemia?

Answer 20

A medical condition characterized by abnormally high levels of nitrogen-containing compounds (such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds) in the blood.

Question 21

Define Hyopcholseriama?

Answer 21

The presence of abnormally low (hypo-) levels of cholesterol in the blood (-emia).

Question 22

What causes megaoesophagus in hypoadrenocorticism?

Answer 22

Megaoesophagus (< 1%)

• due to muscle weakness??
• Drop in Na+ and K+ → drop in membrane potential
• Drop in cortisol associated with muscle weakness
• typically reversible with treatment

Question 23

How can hypoadrenocorticism effect an echocardiogram?

Answer 23

Changes related to hyperkalemia (­increase in K+)

• bradycardia
• peaked T waves
• widened QRS complexes
• Drop in P wave amplitude become progressively smaller
• disappearance of P waves
• ventricular asystole (failure to contract)

Question 24

How is hypoadrenocorticism diagnosed?

Answer 24

Maintain high index of suspicion

• electrolyte abnormalities (Na+:K+ ratio <23)
• however not always abnormal
• lack of stress leukogram in sick dog
• young dog with history of chronic illness
• ACTH stimulation test (ask the adrenal glands to do a job and then they don’t do it huge indication of addisons. Take a blood sample of resting cortisol, inject acth then take post blood sample to measure cortisol= expensive)
• Measure cortisol: flat-line stimulation

Question 25

How should acute hypoadrenocorticism be treated?

Answer 25

**Restoration of intravascular volume/Tx shock** * Tx shock: * Place i.v catheter * Begin 0.9% saline or Hartmann’s solution at 20-90 ml/kg/hr * Assess effectiveness frequently * Once volume restored, reduce rate to maintenance (2ml/kg/hr) * Continue fluids until hydration status, urine output, serum electrolytes and azotaemia are corrected * Regularly accessed every 10-15 mins until vol status improved. * If we stop fluids and Na isn't normal taking away fluids will result in loss of fluid again. **Reversal of hyperkalaemia (if needed)** * Fluid therapy+++ * 10% Calcium gluconate * 0.5- 1ml/kg IV slow over 20 mins * IV dextrose/glucose. 1.0mls/kg 50% (diluted at least 50:50 with saline and ideally given via a central line) * IV soluble insulin (0.25 - 0.5iu/kg IV) with glucose at 2-3g per unit insulin) as will push insulin into cell as it is constransported with glucose. Must follow insulin with glucose to prevent hypoglycaemic crisis. * Sodium bicarbonate (1-2mmol/kg) **Replace lost mineralocorticoids & glucocorticoids** * Dexamethasone (CARE with dose)- as a single dose of approximately 0.1-0.2mg/kg intravenously (potent steroid and only has glucocorticoid activity) * Hydrocortisone (sodium phosphate/succinate) 2-4mg/kg intravenously every 6 hours (most appropriate as has balanced mineralocorticoid and corticoid effect however is very short acting) * Hydrocortisone (sodium phosphate/succinate) at 1mg/ml administered as a continuous infusion of 0.5mg/kg/h * Methylprednisolone sodium 1-2mg/kg intravenously (Correction of any life-threatening arrhythmias)

Question 27

How can long term hypoadrenocorticism be managed?

Answer 27

**Desoxycortone pivalate** * Recently licensed * Mineralocorticoid replacement only * Therefore need to supplement with prednisolone * Given by im injection approx q20-30 days * Effects vary in different dogs so dosage dependent on dog. * Give with pred as well as they need a glucocorticoids.

Question 28

How can long term hypoadrenocorticism be managed?

Answer 28

**Fludrocortisone** * Not licensed * Mineralocorticoid and glucocorticoid replacement * Oral medication * Now very expensive

Question 29

What is the prognosis for hypoadrenocortocism?

Answer 29

Generally good; average survival time of 4 - 5 years

Question 30

What is the haemtological and biochemical profile of addisons?

Answer 30

* Sodium and potassium concentrations; Na/K ratio; * Leucocyte counts (absence of a stress leucogram) * Basal cortisol * ACTH stimulation test; * NORMAL ionised calcium concentrations * Hypercalcaemia may be a result of enhanced absorption of calcium in the gastrointestinal tract, haemoconcentration, decreased GFR from volume contraction and increased complexing and protein binding of calcium. * Lack of cortisol action on renal handling of calcium