Hypoadrenocorticism Flashcards
Hormone
- chemical messenger
- Secreted from a ductless gland
- Emptied directly into the circulation
- Transported by blood to alter the function of a target organ
- Usually has multiple actions
- Present in small concentrations
Relative proportions of each zone of the adrenal gland
- Zona glomerulosa (15%)
- Zona fasciculata (75%)
- Zona reticularis (10%)
- Medulla
Hormone secreted by zona glomerulosa
Aldosterone
Hormone secreted by zona fasciculata
Cortisol
Hormone secreted by zona reticularis
Sex hormones
Hormone(s) secreted by adrenal medulla
Epinephrine and Norepinephrine
Peripheral effects of cortisol
- Vascular tone
- Gluconeogenesis/Glycogenolysis
- Stimulation of erythropoiesis
- Anti-inflammatory
- Adaptation to stress
What system regulates Aldosterone?
- RAAS
What is aldosterone released in response to?
- Hypovolemia, hyponatremia, hyperkalemia
- Via Angiotensin II
Primary functions of Aldosterone (electrolytes)
- Increased sodium and chloride reabsorption (SAVE SODIUM)
- Increased potassium and hydrogen secretion (PEE POTASSIUM)
Primary (adrenal gland lesion) cause of hypoadrenocorticism (#1 cause)
- Immune mediated destruction of adrenal cortex
How much of the adrenal cortex must be destroyed for clinical signs (usually)?
- > 85-90% of adrenal cortical destruction
- Most cases are 95%
Other primary (adrenal gland lesion) causes of hypoadrenocorticism
- Iatrogenic destruction
- Drugs (mitotane, trilostane)
- Suppression by exogenous steroids
- Neoplasia
- Granulomatous disease
Secondary causes of hypoadrenocorticism (Pituitary gland lesion)
- RARE
- Decreased ACTH
Typical Addisonian
- Destruction of zona glomerulosa and fasciculata
- Deficiency of cortisol (glucocorticoid) and aldosterone (mineralocorticoid)
Atypical Addisonian
- Destruction of zona fasciculata only (?)
- Signs of cortisol deficiency only
- No electrolyte changes
- This is why you can’t rule out Addison’s even if you don’t see changes in electrolytes
Does atypical really exist?
- May be another mechanism allowing for maintenance of electrolytes even without aldosterone present
Typical age of Addisonian patients
Young to middle aged
Typical sex of Addisonian patients
Females may be more predisposed
Typical breeds of Addisonian patients
- Standard poodles***
- Portuguese water dog
- Nova Scotia Duck Tolling Retriever
- Bearded Collie
- Others: Great Danes, Westie, Saint Bernard, etc.
Acute signs of Addisonian crisis
- May present recumbent, shocky
- Threatening crisis
Chronic signs of Addison’s
- “waxing and waning”
- History of GI signs, etc., that resolve on their own with supportive care (especially fluids)
- PU/PD, weakness/lethargy, weight loss
Physical exam findings of Addison’s
- Non-specific findings
- Changes may be vague or absent
- Weakness, dehydration, pale mucous membranes, decreased pulse strength, bradycardia, hypothermia
Most common CBC changes with Addison’s
- No stress leukogram (92%)
- Eosinophilia (20%)
- Lymphocytosis (10%)
- Non-regenerative anemia (27%) - may be masked by dehydration
Pathophysiology of non-regenerative anemia in Addison’s
- Steroids play a role in erythropoiesis, so chronically can have an anemia
Common Urinalysis in Addison’s
- Isosthenuria even with dehydration (60%)
Pathophysiology of isosthenuria in Addison’s
- Medullary washout due to low sodium
Common chemistry panel findings in Addison’s
- Hyponatremia
- Hyperkalemia
- Azotemia
- Hyperphosphatemia
Less common chemistry panel findings in Addison’s
- Hypercalcemia (unknown mechanism)
- Hypoalbuminemia (GI loss, possible hepatopathy)
- Hypoglycemia (lack of glucocorticoids)
- Hypocholesterolemia (melena, GI signs can lead to hypocholesterolemia)
- Elevated liver enzymes
Clinical signs of Addison’s associated with Cortisol deficit
- Vomiting Diarrhea
- Hypoglycemia
- Maintenance of vascular tone
Clinical signs of Addison’s associated with Aldosterone deficit
- Polyuria/polydipsia (possible some contribution from glucocorticoids)
- Hyperkalemia
- Hyponatremia
General signs of Addison’s that are a combination of the Aldosterone and Cortisol signs
- Lethargy/Weakness
- Collapse
- Hypovolemic shock
Na:K ratio with Addison’s
- K is high and Na low with “Typical Addison’s” (Na:K ratio <27)
- Electrolytes normal with “Atypical Addison’s (can still progress to clinical form)
- There are other things that can cause a ratio <27 (NOT PATHOGNOMONIC)
Baseline cortisol <2 µg/dL Meaning
- If cortisol <2 µg/dL = NOT DIAGNOSTIC - need ACTH stimulation to confirm
- YOU WOULD HAVE TO COMMIT TO STIM-ING THE ANIMAL!
- Very suspicious but NOT diagnostic
Baseline cortisol >2 µg/dL Meaning
- NOT Addison’s
ACTH stim overview for Addison’s
- Gold standard
ACTH Stim Test Protocol
- Give cosyntropin IV and measure cortisol 1 hr post administration
ACTH Stimulation tests consistent with Addison’s
- Most Addisonian patients have pre and post cortisol values <1 µg/dL
- Value <2 µg/dL = Addison’s
- Value >2 µg/dL = Not Addison’s
Treatment for Acute Addisonian crisis
- IV fluids, supportive, and symptomatic care
- Get all blood work and perform an ACTH stim test
- If you are suspicious of Addison’s and patient is unstable, then start glucocorticoids
- Ideally perform stim first, but if you can’t then use dexamethasone (NOT PRED)
Rationale for fluids in Addison’s
- Volume replacement
- Fluids will likely also help correct electrolyte imbalances
- Be cautious about correcting sodium too rapidly
- Wait until sodium levels are safe to administer a mineralocorticoid (otherwise you can correct sodium too quickly, which is also dangerous)
How long will treatment for Addison’s last?
- LIFELONG TREATMENT NEEDED
What are the mainstays of treatment for chronic Addison’s?
- Glucocorticoids (prednisone): oral
- Mineralocorticoid (DOCP or Percortin): IM injection
- Glucocorticoid and Mineralocorticoid (Florinef): oral
Prednisone treatment for Addison’s
- Daily administration
- Give at physiologic doses (~0.1-0.25 mg/kg/day)
- Increase dose during stressful or exciting events
DOCP treatment frequency
- Given every 25-30 days
Price of DOCP
- $$$$$
Florinef frequency
- Daily
Florinef overview
- Fludricortisone acetate
- Glucocorticoid and mineralocorticoid
- Difficult to manipulate tablet size
Florinef challenges
- Can be difficult to accurately dose for glucocorticoid amount
- May be too much for some
- Others may need additional prednisone
Florinef cost
- Often less expensive than DOCP
Monitoring for DOCP
- Check electrolytes 14 days after starting
- Then check every 25-30 days to determine maximal duration possible between injections
- Once controlled - check electrolytes every 6 months
Glucocorticoid monitoring
- Based on clinical signs
- If pred side effects seen (PU/PD, polyphagia), may need to decrease dose
- If GI signs then may be too low
Prognosis of Addison’s
- Good
- Quality of life can be excellent with vigilance and proper care
- Medications need to be given correctly and on schedule to prevent crisis and possible death
- Can be cost prohibitive as medications are expensive
