Hypoadrenocorticism Flashcards
Ettinger Ch 296
What are the 3 layers of the adrenal cortex (outside to inside)?
z. glomerulosa - salt
z. fasiculata - sugar
z. reticularis - sex
Which layer(s) of the adrenal cortex is/are responsible for the production of glucocorticoids?
z. fasiculata
z. reticularis
What regulates the production of mineralecorticoids (i.e., what stimulates production)?
ACTH
hyponatremia
hyperkalemia
angiotensin II (AngII)
What are examples of androgens that are produced by z. reticularis?
dehydroepiandrosterone (DHEA)
androstenedione
What is the precursor molecule for all adrenocrotical hormones?
cholesterol
Which is the only cortical layer that contains aldosterone synthase?
z. glomerulosa
Hypoadrenocortisim (HA) in humans is a rare autoimmune disorder thought to be related to the destruction of the adrenal cortex due to antibodies against ___________, which is present in all 3 layers.
21-hydroxylase
T/F: Similarly in humans, dogs have antibodies directed against 21-hydroxylase, which causes the autoimmune destruction of the adrenal gland.
F - 21-hydroxylase has not been identified in dogs. Instead, P450 enzyme antibodies have been documented in 24% of dogs with HA.
Familial HA has been reported in which breeds?
Leonbergers
Pomeranians
Great Danes
Standard Poodles
Bearded Collies
Which two drugs have been reported as a rare cause of HA?
ketoconazole
phenobarbital
What two drugs are associated with primary transient or permanent iatrogenic HA?
mitotane
trilostane
T/F: Primary Addison’s disease is more common and is most often associated with infiltrative disease (neoplasia, inflammation, infectious, infarct, trauma).
F - Primary Addison’s (failure of the adrenal cortex) is the most common form; however, it is rarely the result of destructive/infiltrative disease. This is more common in secondary Addison’s disease (pituitary and/or hypothalamus).
Secondary HA is rare and is often due to an infiltrative process that results in the impaired secretion of _________ and/or ______.
ACTH (adrenocorticotropic hormone)
CRH (corticotropin-releasing hormone)
T/F - Secondary HA rarely causes electrolyte derangement.
T - RAAS is independent of pituitary or hypothalamic control.
T/F - A sequelae of a hypophysectomy is primary HA.
F - Addison’s is a sequelae of a hypophysectomy surgery; however it would be due to iatrogenic secondary HA causing a low/ absent ACTH secretion.
T/F - Chronic exogenous corticosteroid administration causes decreased ACTH secretion, resulting in bilateral adrenal atrophy.
T -
Hypoadrenocortisim - Signalment
young to middle aged dogs, 3-4 years, but can be seen as young as 2 months and as old as 12 years
Hypoadrenocortisim - Clinical signs (name at least 2 more other than vomiting and diarrhea)
anorexia
weight loss
vomiting
diarrhea
lethargy
weakness
PU/PD
shaking
collapse
T/F - Hematemesis or melena without hematochezia are common in dogs with HA.
F - Noted in 11% of dogs with HA
What are some functions of glucocorticoids, specifically to GI?
Glucocorticoids are needed for healthy gastric mucosal blood pressure, temperature and glucose concentrations. They are also important for maintaining the mucosal gastric barrier responsible for providing protection from its acidic contents (i.e. Buddy).
Why do some dogs with Addison’s experience PU/PD?
Mineralocorticoids promote sodium reabsorption in the distant convoluted tubules (DCT) and potassium excretion into the urine.
Lack of mineralocorticoids causes osmotically active soidum loss in the urine resulting in hyponatremia (water follows) leading to PU and compensatory PD.
Hypoadrenicortisim - Physical exam
mild to severe
dehydration
hypotension
bradycardia
weak pulses
weakness
underweight/ weight loss
abdominal pain
hypovolemic/hypotensive shock
seizures
Uncontrolled Addison’s disease can lead to hypotensive shock (mean SBP of 90 mmHg). Explain the pathophysiology of hypotension in dogs with Addison’s disease.
Lack of glucocorticoids
Urine losses of free water
vomiting, diarrhea
lack of oral intake
T/F - Tachycardia is a common finding in dogs with Addison’s disease.
F - Bradycardia can be common due to hyperkalemia. Hyperkalemia can lead to potassium retention in cardiac muscles. This interferes with outward K current needed for the final rapid repolarizaiton of cardiac action potentials, ultimately slowing down conduction.
T/F - Severe azotemia, hypoalbuminemia and/or increased liver enzymes are usually completely reversible in dogs with HA.
True
Functions of aldosterone, name 3
Sodium reabsorption into the DCT
Potassium excretion into the urine
Hydrogen ion secretion into the urine
Why do some dogs with Addison’s disease experience an acidemia?
Aldosterone facilitates hydrogen ion secretion into the urine. Deficiency of aldosterone can lead to acidemia.
Hypoadrenocortisim - Common clin path findings
Pre-renal azotemia
hypoNa, hyperK (>80%)
Na/K <24
Acidemia (d/t aldosterone deficiency)
Hypochloremia (40-60%)
Hypercalcemia (total and ionized)
Mild hypoglycemia (<20%)
Increased ALT and AST (poor liver perfusion, ischemic damage to hepatocyte)
Hypoalbuminemia, hypocholesterolemia (acute effects of GI hypoperfusion)
Isosthenuria (hyponatremia decreasing renal concentration gradient)
What are 2 potential mechanisms of Addion’s disease that can cause hypercalcemia?
Glucocorticoids promote calciuresis, their deficiency may contribute to hypercalcemia.
Acidemia may increase ionized calcium concentrations due altered albumin binding (excessive H+ compete for albumin)
T/F - Megaesophagus has been reported in humans with HA.
T - but no clear association between ME and HA in dogs
ECG findings consistent with hyperkalemia
short/absent P waves
prolonged PR
wide QRS
Short R
Tall T’s
ectopic beats
How do you run an ACTH stim test (logistics)?
- Measure serum cortisol (baseline)
- Give synthetic short-acting ACTH (cosyntropin) 1-5 mcg/kg
- Measure cortisol 1 hour later
Ddfx - “pseudo-Addison’s disease”
tirhcuriasis
salmonellosis
ill pregnant dogs
chylothorax
In patients experiencing an Addisonian crisis, fluid therapy is the single most important treatment for an acute crisis. Which fluid type is generally recommended?
0.9% NaCl - contains more NaCl and less K than other crystalloids
Correcting hyponatremia:
-Should not exceed more than _____ within the first 2-3 hours.
-Should not exceed more than _____ in the first 24 hours.
1-2mEq/L (1-2mmol/L)
8-12 mEq/L (8-12 mmol/L)
Emergency dextrose dose
0.25-0.5 g/kg diluted 1:3
_______ can be used in the long-term management of Addison’s disease and contains both gluco- and mineralocorticoids.
Fludricortisone
What is the ideal Na/K ratio when monitoring an Addisonian for the long-term?
30-32, no lower than 28 no higher than 32
