Canine hypoadrenocorticism Flashcards
Describe the anatomy of the adrenal cortex?
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.
Draw a flow diagram detailing glucocorticoid release and it’s feedback mechanisms?
Describe the actions glucocorticoids?
- Part of the “fight or flight” response
- A “stress” hormone
- Counteracts the effects of stress
- Essential for life!
Describe aldosterone regulation?
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
What is the function of aldosterone?
- 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
What is primary hypoadrenocorticism and what is it also known as?
- 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
What are some of the causes of primary hypoadrenocorticism in canines?
Idiopathic atrophy
- probably immune-mediated destruction
- associated with other endocrinopathies
Iatrogenic
- drugs: mitotane, trilostane
- surgery: bilateral adrenalectomy
What is Secondary Hypoadrenocorticism?
- Pituitary stops producing ACTH
- Deficiency of ACTH
- Usually only cortisol deficient (electrolytes normal)
- Rare
What is Iatrogenic hypoadrenocorticism?
- 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
What is the signalment of canine hypoadrenocorticism?
- Young-middle aged dogs. Median age 4-6 years
- 70% females
- Any breed, but certain breed predispositions
- (Extremely rare in cats)
Breeds with an increased risk of hypoadrenocorticism include:
- 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)
What does pathognomonic mean?
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.
What is the pathophysiology of hypoadrenocorticism?
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
What are the clinical signs of chronic hypoadrenocorticism?
- 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
What are the clinical signs of acute hypoadrenocorticism?
- 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
What is the biochemical profile of hypoadrenocorticism?
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
What causes megaoesophagus in hypoadrenocorticism?
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
How can hypoadrenocorticism effect an echocardiogram?
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)
How is hypoadrenocorticism diagnosed?
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
How should acute hypoadrenocorticism be treated?
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)
How can long term hypoadrenocorticism be managed?
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.
How can long term hypoadrenocorticism be managed?
Fludrocortisone
- Not licensed
- Mineralocorticoid and glucocorticoid replacement
- Oral medication
- Now very expensive
