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Primary adrenocortical insufficiency (Addison's): Hypoadrenocorticism …
Primary
adrenocortical insufficiency (Addison's): Hypoadrenocorticism
Destruction of adrenal cortex
specifically destroyed
glucocorticoid secreting cells
mineralocorticoid secreting cells
Idiopathic
atrophy/Autoimmune Injury
inflammation
infarcts
Neoplastic metastases
Amyloid
Drugs
Mitotane (0'P'-DDD)
Trilostane
Clinical Features - Primary
Signs nearly always are due to combined effects of aldosterone and cortisol deficiencies
gradual onset
Stress may precipitate an adrenal crisis
Waxing and waning course
response to supportive care is common
Pathophysiology
Mineralocorticoid Deficiency
Inability to conserve sodium and excrete K+
1. Hyponatremia
2. Hypochloremia
3. Hyperkalemia
Impairs neuromuscular excitability and leads to myasthenia, bradycardia
Renal and GI electrolyte and water losses
severe dehydration
hypovolemia
hypotension
Volume contraction leads to < cardiac output (microcardia)
< GFR-->
prerenal azotemia
metabolic acidosis
Cortisol Deficiency
GI Signs:
Anorexia
Dysphagia (cats)
Vomiting
Abdominal Pain
Weight Loss
Mental Changes
Depression
lethargy
Hematologic Abnormalities
Anemia- Non-regenerative
Eosinophilia
- relative vs absolute
Lymphocytosis
Hypercalcemia
Hypoglycemia
Impaired tolerance to stress
Hypoalbuminemia
Clinical Findings
Dogs
4mo -12yr
F=70%
All breeds
rare in cats
Likely genetic influence in:
Standard poodles
Labrador retrievers
Bearded Collies
Leonbergers
Nova Scotia Duck Tolling dogs
Portuguese water spaniels
West Highland White Terriers
The Risks of Ratios
Normal Na/K ratio does not exclude Addison's
Secondary hypoadrenocorticism
Mild early primary hypoadrenocorticism
Animals treated prior to sampling
Abnormal Na/K ratios do not = Addison's
Urinary Tract Diseases
Anuric
/Oliguric renal failure
Post-renal
obstruction
Rents
in the excretory pathway
Other causes for > K+
Metabolic Acidosis
Drug administration:
Potassium sparing diuretics
Ace inhibitors
K+ supplementation to fluids
Aortic thrombosis in cats
Whipworms - puppy
Pseudohyperkalemia
Asian Breeds -
high RBC potassium released on clotting blood
Severe leukocytosis: > 100,000/µl
Severe thrombocytosis: > 1,000,000/µl
Therapy
ACUTE CRISIS
treat until they respond or when the diagnosis is refuted!
It
does not hurt patients
with renal failure or diarrhea to
initially
receive isotonic fluids, dextrose or bicarbonate.
Addison's patients
die if untreated
Goals
Correct
hypovolemia and hypotension
Immediate volume replacement
a.
0.9% saline
(potassium free)
20-40 ml/kg in first 1 to 2 hrs
follow with maintenance rates
b. Collect blood and serum and UA prior to Rx
c.
Collect resting and post ACTH cortisol samples
(use
dexamethazone
if steroids given)
needs are 2 to 10 times maintenance in stress
Dexamethazone phosphate
Provide
exogenous glucocorticoids
Decrease parenteral dosages slowly to maintenance
b. Continue parenteral drug until blood volume replaced and vomiting has stopped
(prednisone
0.5-1mg/kg/day = anti-inflammatory
)
(prednisone
2-4mg/kg/day = immunosuppressive
)
a.
~ 0.2 mg/kg/day
of prednisone (
physiologic
)
Reverse
electrolyte
imbalances
Rapid
NaCl infusion
will decrease serum potassium
a. Dilutional effect
b. > Renal perfusion
c. EKG improvement in 30 to 60 min.
d. Add
5% dextrose helps move K intracellularly
e. In severe cases, adding regular insulin IM (with IV dextrose) will aid intracellular movement of potassium.
f. (IV bicarbonate decreases potassium if above not effective)
g. Also if close to asystole can give calcium gluconate (cardioprotective but does not decrease glucose)
Manage
acidosis and hypoglycemia
Rarely
necessary to correct acidosis if adequate fluid resuscitation is provided.
Mineralocorticoid Replacement
Percortin-V
desoxycorticosterone pivalate
DOCP
:
2.2 mg/kg IM q 25 days package label
Many clinicians extend to 28-31 days/monthly
Maintenance Therapy
1.Most dogs require 24 to 48 hrs of IV fluids and injectable steroids to stabilize.
In cats it may be 3 to 5 days after initiating therapy before significant clinical improvement is noted.
Oral Therapy:
Fludrocortisone acetate (Florinef) - potent mineralocorticoid and glucocorticoid. 0.1 mg/ 5 to 10 kg divided BID.
Prednisone occasionally needed - 0.2 mg/kg daily, divided. Have available at all times.
Therapy can be less expensive than DOCP for large dogs
Injectable DOCP
DOCA Pivalate once every 25 days o (PercortinV).
Supplemental prednisone often is needed. Always start with it – physiologic dose.
Owner compliance is critical.
Monitor electrolytes monthly
CS
Hypercalcemia
Severity parallels severity of disease
Range: 12-15 mg/dl, X= 13.2 (30% of dogs)
Responds rapidly to glucocorticoids
Confuses the diagnosis!
Acid-Base Abnormalities
Mild metabolic acidosis is common
- 45%
Decreased renal excretion of H+
Impaired HCO3 reabsorption
Decreased GFR
Hypovolemia
Renal Abnormalities
Prerenal azotemia
is common
93%Dogs,
100% Cats
mean BUN = 83 mg/dl
Primary ischemic injury may also develop
Usg = < 1.030 in most
Hypoalbuminemia
Occasional finding in dogs with hypoadrenocorticism.
Mechanism speculative
Cortisol augments
hepatic
albumin synthesis
Appears to be
cortisol responsive
EKG Abnormalities!
EKG can be efficient method for detecting hyperkalemia if > 5.5 meq/L, and for monitoring response to therapy
Progressive changes in the EKG
5.5 meq/L
tall, peaked T-waves
6.5 meq/L
prolonged QRS
7.0 meq/L
< P-wave
amplitude and duration, prolonged PR interval
8 - 8.5 meq/L
atrial arrest, absent P-wave,
bradycardia, S-T depression
11.0-14 ventricular
asystole, fibrillation
Plasma Cortisol Assays
Resting Cortisol
Excellent
screening
test in sick dogs where Addison’s is a rule-out
Resting cortisol of
< 1.0 µg/dl
have 100% sensitivity and 98% specificity
Resting cortisol
> 2.0 µg/dl
rule-out the diagnosis without ACTH stimulation testing
Resting between < 2 µg/dl – do STIM
ACTH Stimulation Testing
= Gold Standard
ACTH gel - zero and 2 hrs post
Synthetic ACTH - 0 and 1 hr post.
Expensive drug costs
Prednisone/Prednisolone
cross react
with cortisol assays
use dexamethazone if treating prior to diagnostic tests
Plasma ACTH Results (Primary or Secondary)
Normal to low resting, cortisol, and minimal or no response following ACTH
Plasma ACTH assay necessary to distinguish primary from secondary Addison's (but there can be overlap)
a. Plasma ACTH often very
high in primary
b. Plasma ACTH often
low or non-detectable in secondary
hypoadrenocorticism