Hypoadrenocorticism

Question 1

OBJ: Understand adrenal gland functional anatomy and regulation

Answer 1

• see picture

Question 2

OBJ: Understand the pathological bases for Hypoadrenocorticism

Answer 2

• Destruction of adrenal cortex
  
  • immune-mediate adrenalitis/adrenal atrophy (most common)
    
    • lowers GC and MC production
  • Infiltrative diseases (granuloma, amyloidosis
    
    • same size /bigger gland but decreased functional ability
• Adrenal suppression by exogenous GC’s
  
  • Iatrogenic
  • adrenal gland can shrink due to disuse

Question 3

OBJ: Know the clinical signs and laboratory findings of Hypoadrenocorticism

Answer 3

• Waxing and waning illness
• Loss of appetite - weight loss
• lethargy/depression
• Vomiting/diarrhea
• PU
• weakness
• Regurgitation/abdominal pain
• Mild anemia
• lack of stress leukogram
• Azotemia
• Electrolyte abnormalities
  
  • usually hyponatremia and hyperkalemia
    
    • Na+/K+ ratio <27:1
• dilute USG

Question 4

OBJ: Understand the diagnostic approach to Hypoadrenocorticism

Answer 4

• ACTH stimulation test
  
  • synthetic ACTH used
  • Dogs with Addisons show no increase in cortisol after admin
    
    • their adrenal gland does not work so there is no response to the extra ACTH

Question 5

OBJ: Know and understand the treatment of a patient with Hypoadrenocorticism

Answer 5

• Fix crisis
  
  • glucocorticoid, mineralocorticoid both injectable
• Maintain healthy
  
  • can move to long lasting oral glucocorticoid and mineralocorticoid
• Monitor for life:
  
  • electrolyte balance
  • clinical signs

Question 6

Which hormones are released from the adrenal gland? give specific areas and examples

Answer 6

Question 7

How is cortisol secretion regulated?

Answer 7

• ACTH secretion is pulsatile
• ACTH secretion influenced by:
  
  • feeding
  • Physiologic / environmental stress
    
    • pain, trauma, hypoxia, pyrogens, cold exposure, surgery
• HYPERadrenocorticism - excess cortisol
• HYPOadrenocorticism - cortisol and aldosterone deficiency

Question 8

What are the two types of hypoadrenocorticism? how are they different?

Answer 8

Question 9

What are causes of adrenal cortex destructuion?

Answer 9

• Immune-mediated adrenalitis / adrenal atrophy
  
  • most common - possibly genetic?
• Infiltrative diseases (ex granuloma, amyloidosis)

Question 10

What are the results of adrenal suppression by exogenous Glucocorticoids?

Answer 10

Usually GC deficiency, sometimes aldosterone deficiency

Question 11

What are the consequences of Adrenal Failure?

Answer 11

• See signs at 85% loss
• Cortisol deficiency - multisystemic
  
  • inappetence, weight loss, lethargy, GI signs, hypoglycemia, hypercalcemia
• Aldosterone deficiency - salt and water
  
  • Electrolyte disturbances
    
    • hypoNa, HypoCl, HyperK
  • Decreased plasma volume
  • Polyuria and inc water loss

Question 12

What affects does a cortisol deficiency have on the body?

Answer 12

• Multisystemic
  
  • Inappetence
  • Weight loss
  • Lethargy
  • GI signs
  • hypoglycemia
  • Hypercalcemia

Question 13

What affects does aldosterone deficiency have on the body?

Answer 13

• Salt and water affects:
  
  • Electrolyte disturbances
    
    • Hyponatremia, hypocloremia, hyperkalemia
  • Decreased plasma volume
  • Polyuria and increased water loss

Question 14

What are the patient factors that can play a role in hypoadrenocorticism?

Answer 14

• “young dog” disease
  
  • mean age 4.5yo @ diagnosis
• Genetic influences based on:
  
  • breed susceptibility, pedigree analysis, genomic studies
• In early stages - basal hormone secretion is sufficient unless stressed
  
  • may be “ill” with non-specific signs
  • “waxing and waning”

Question 15

What are the most common signs of hypoadrenocorticism?

Answer 15

• Loss of appetite
• Lethargy/depression
• vomiting / diarrhea
• Polyuria
• Weakness
• Weight loss
• Regurgitation / abdominal pain

Question 16

What is an “Addisonian crisis”

Answer 16

• Severe hypoadrenocorticism
• Progression of disease
• Severe signs caused be electrolyte distrubances and volume depletion
  
  • Bradycardia
  • Weak pulses
  • Poor perfusion
  • Hypothermia
  • Shock
  • Melena
  • Collapse
  • Seizure

Question 17

What changes are seen on a CBC of a patient with hypoadrenocorticism?

Answer 17

• Mild anemia
• Lack of a ‘stress leukogram’
  
  • important observation in a ‘critical’ patient

Question 18

What changes are seen on serum chemistry of a patient with hypoadrenocorticism

Answer 18

• Azotemia - elevated BUN and creatinine
• Electrolyte abnormalities
  
  • Hyponatremia and hypochloremia - aldosterone deficiency
  • Hyperkalemia - aldosterone deficiency and acidosis
  • Addison’s usually causes both!
• Na+/k+ ration (normal > 27:1)
  
  • < 27:1 is suspicious; < 20:1 strongly suspicious
• Other: hypoglycemia, hypercalcemia, hypoalbuminemia, acidosis

Question 19

What changes on a urinalysis are seen in a patient with hypoadrenocorticism? Why?

Answer 19

• USG often dilute (<1.030) despite dehydration
  
  • Aldosterone deficiency - Sodium and Chloride losses cannot take place without concurrent loss of water

Question 20

What is hypoadrenocorticism commonly misdiagnosed as? why?

Answer 20

• Renal failure
  
  • Azotemia + dehydration + dilute urine

Question 21

How can a diagnosis of hypoadrenocorticism be confirmed?

Answer 21

• ACTH stimulation test
  
  • Dogs with Addison’s show NO increase in cortisol after administration of exogenous ACTH
  • Affected dogs usually have a “flat stim” test
    
    • low baseline cortisol and low cortisol after ACTH

Question 22

are aldosterone levels assessed in Addison’s patients?

Answer 22

• NO
  
  • deficiency is inferred by electrolyte abnormalities

Question 23

What are some infrequently used tests for Hypoadrenocorticism?

Answer 23

• Endogenous ACTH
  
  • elevated in primary hypoadrenocorticism but not used for diagnosis
• Basal (resting) cortisol level
  
  • used to screen suspicious cases for hypocortisolemia
  • low result is consistent with hypoadrenocorticism but NOT DIAGNOSTIC
• Aldosterone concentration
  
  • Not routinely measured; can confirm mineralocorticoid deficiency
  • Aldosterone overlaps between normal dogs and dogs with hypoadrenocorticism
  • Basal and ACTH-stimulated samples measured
  • Occasionally used in elevation of atypical disease

Question 24

What is the treatment for Hypoadrenocorticism?

Answer 24

• Initial hormone replacement
  
  • patient is dehydrated, inappetence and in crisis
  • Glucocorticoid - usually injectables
  • Mineralocorticoid
    
    • Na containing crystalloid - replaces volume
    • Improves BP
• Maintenance hormone replacement
  
  • Patient is stable, hydrated, eating
  • Glucocorticoid - oral
  • Mineralocorticoid supplement
    
    • injectable long-acting product
    • Oral Product
• Glucocorticoid replacement:
  
  • Acute therapy - use injectable glucocorticoid
    
    • Dexamethasone 0.05 - 0.1 mg/kg IV
    • Prednisolone sodium succinate (alternative)
  • Chronic therapy - daily therapy with oral glucocorticoid
    
    • Prednisone - Physiologic dose is 0.2 - 0.4 mg/kg/day
    • Increase dose if anticipate stressful event
    • Can safely double dose for several days
    • Only treatment needed for atypical Addison’s Disease
• Mineralocorticoid Replacement
  
  • Administer immediately after diagnosis
  • Maintenance therapy for life
  • DOCP - Deoxycorticosterone pivalate
    
    • 2.2 mg/kg IM or SC every 21-30 days
    • Max dose 50mg/dog/dose
    • Slow release of mineralocorticoid
    • No GC activity
    • Single dose is not harmful if dog does not have Addison’s
  • Fludrocortisone (Florinel®)
    
    • Has minor GC activity
    • Dose 0.015 - 0.02 mg/kg/day
    • Poor absorption
    • ~50% of dogs treated with fludrocortisone will not require additional GC

Question 25

What long term monitoring has to be done for patients with hypoadrenocorticism?

Answer 25

* Serial evaluation of electrolytes * First month after diagnosis; weekly beginning 2-weeks after first DOCP dose * As needed until the patient's effective dose and interval is determined * Every 3 - 4 months thereafter * Adjust mineralocorticoid dose and dosing interval based on electrolyte results * Serial evaluation of clinical signs * Owners' observation helpful * Deficiencies result in subtle manifestations * If not “ doing quite right” adjust daily GC dose * MC adjustment if GC adjustment doesn't correct * No Role for serial ACTH stim tests

Question 26

How can we reduce the cost of treating hypoadrenocorticism patients for owners?

Answer 26

* Get good control * Reduce hospital costs * Healthy patient * Work to find minimal effective dose * Shop around for best price * on-line vet pharmacies * Owner administers DOCP at home * must be part of long-term monitoring program with veterinarian

Question 27

What is the treatment for an Addisonian Crisis?

Answer 27

* Volume replacement * death due to vascular collapse and shock * Restore volume using 0.9% NaCl * Avoid rapid replacement if Na is \<125 mEq/L * Hormone replacement after initial fluid bolus * Glucocorticoid replacement - complete ACTH stim test before GC are given * Mineralocorticoid replacement * Treat hyperkalemia if needed * administer calcium gluconate * Treat acidosis if needed * administration of bicarbonate * rarely needed

Question 28

How is hyperkalemia treated during an Addisonian crisis?

Answer 28

* Specific therapy usually not needed * often corrects with volume replacement and increased urine production * Severe or life-threatening hyperkalemia requires immediate treatment * Signs include bradycardia and arrhythmia * Options: * 10% Calcium gluconate * 0.5 - 1.0 mg/kg IV SLOW over 10 - 20 minutes with continuous ECG monitoring * 15 - 30 minutes for onset of action * Cardioprotective effect - protects against K⁺ but doesn't directly reduce serum K⁺ * Dextrose + Humulin-R (regular insulin) * 1 - 2 mls/kg of 50% dextrose IV and 0.125 - 0.5 units regular insulin/kg IV * follow with glucose CRI

Question 29

What is the prognosis of canine Hypoadrenocorticism?

Answer 29

* Excellent * if owners are educated * compliance is excellent * close follow-up is maintained

Question 30

What is the Etiology of feline Hypoadrenocorticism?

Answer 30

* Primary - rare * suspected to be immune-mediated * Secondary * iatrogenic causes * adrenal suppresion due to megestrol acetate or glucocorticoids

Question 31

How if Feline Hypoadrenocorticism diagnosed?

Answer 31

* ACTH stimulation test * 0.125mg/cat * blood samples taken before, 30 and 60 minutes post injection

Question 32

How are canine and feline Hypoadrenocorticism similar?

Answer 32

* similar clinical signs * similar laboratory abnormalities * similar treatments