Hypoadrenocorticism

Question 1

What are the 3 layers of the adrenal cortex (outside to inside)?

Answer 1

z. glomerulosa - salt
z. fasiculata - sugar
z. reticularis - sex

Question 2

Which layer(s) of the adrenal cortex is/are responsible for the production of glucocorticoids?

Answer 2

z. fasiculata
z. reticularis

Question 2

What regulates the production of mineralecorticoids (i.e., what stimulates production)?

Answer 2

ACTH
hyponatremia
hyperkalemia
angiotensin II (AngII)

Question 2

What are examples of androgens that are produced by z. reticularis?

Answer 2

dehydroepiandrosterone (DHEA)
androstenedione

Question 3

What is the precursor molecule for all adrenocrotical hormones?

Answer 3

cholesterol

Question 4

Which is the only cortical layer that contains aldosterone synthase?

Answer 4

z. glomerulosa

Question 5

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.

Answer 5

21-hydroxylase

Question 6

T/F: Similarly in humans, dogs have antibodies directed against 21-hydroxylase, which causes the autoimmune destruction of the adrenal gland.

Answer 6

F - 21-hydroxylase has not been identified in dogs. Instead, P450 enzyme antibodies have been documented in 24% of dogs with HA.

Question 7

Familial HA has been reported in which breeds?

Answer 7

Leonbergers
Pomeranians
Great Danes
Standard Poodles
Bearded Collies

Question 8

Which two drugs have been reported as a rare cause of HA?

Answer 8

ketoconazole
phenobarbital

Question 9

What two drugs are associated with primary transient or permanent iatrogenic HA?

Answer 9

mitotane
trilostane

Question 10

T/F: Primary Addison’s disease is more common and is most often associated with infiltrative disease (neoplasia, inflammation, infectious, infarct, trauma).

Answer 10

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).

Question 11

Secondary HA is rare and is often due to an infiltrative process that results in the impaired secretion of _________ and/or ______.

Answer 11

ACTH (adrenocorticotropic hormone)
CRH (corticotropin-releasing hormone)

Question 12

T/F - Secondary HA rarely causes electrolyte derangement.

Answer 12

T - RAAS is independent of pituitary or hypothalamic control.

Question 13

T/F - A sequelae of a hypophysectomy is primary HA.

Answer 13

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.

Question 14

T/F - Chronic exogenous corticosteroid administration causes decreased ACTH secretion, resulting in bilateral adrenal atrophy.

Answer 14

T -

Question 15

Hypoadrenocortisim - Signalment

Answer 15

young to middle aged dogs, 3-4 years, but can be seen as young as 2 months and as old as 12 years

Question 16

Hypoadrenocortisim - Clinical signs (name at least 2 more other than vomiting and diarrhea)

Answer 16

anorexia
weight loss
vomiting
diarrhea
lethargy
weakness
PU/PD
shaking
collapse

Question 17

T/F - Hematemesis or melena without hematochezia are common in dogs with HA.

Answer 17

F - Noted in 11% of dogs with HA

Question 18

What are some functions of glucocorticoids, specifically to GI?

Answer 18

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).

Question 19

Why do some dogs with Addison’s experience PU/PD?

Answer 19

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.

Question 20

Hypoadrenicortisim - Physical exam

Answer 20

mild to severe
dehydration
hypotension
bradycardia
weak pulses
weakness
underweight/ weight loss
abdominal pain
hypovolemic/hypotensive shock
seizures

Question 21

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.

Answer 21

Lack of glucocorticoids
Urine losses of free water
vomiting, diarrhea
lack of oral intake

Question 22

T/F - Tachycardia is a common finding in dogs with Addison’s disease.

Answer 22

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.

Question 23

T/F - Severe azotemia, hypoalbuminemia and/or increased liver enzymes are usually completely reversible in dogs with HA.

Answer 23

True

Question 24

Functions of aldosterone, name 3

Answer 24

Sodium reabsorption into the DCT Potassium excretion into the urine Hydrogen ion secretion into the urine

Question 25

Why do some dogs with Addison's disease experience an acidemia?

Answer 25

Aldosterone facilitates hydrogen ion secretion into the urine. Deficiency of aldosterone can lead to acidemia.

Question 26

Hypoadrenocortisim - Common clin path findings

Answer 26

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)

Question 27

What are 2 potential mechanisms of Addion's disease that can cause hypercalcemia?

Answer 27

Glucocorticoids promote calciuresis, their deficiency may contribute to hypercalcemia. Acidemia may increase ionized calcium concentrations due altered albumin binding (excessive H+ compete for albumin)

Question 28

T/F - Megaesophagus has been reported in humans with HA.

Answer 28

T - but no clear association between ME and HA in dogs

Question 29

ECG findings consistent with hyperkalemia

Answer 29

short/absent P waves prolonged PR wide QRS Short R Tall T's ectopic beats

Question 30

How do you run an ACTH stim test (logistics)?

Answer 30

1. Measure serum cortisol (baseline) 2. Give synthetic short-acting ACTH (cosyntropin) 1-5 mcg/kg 3. Measure cortisol 1 hour later

Question 31

Ddfx - "pseudo-Addison's disease"

Answer 31

tirhcuriasis salmonellosis ill pregnant dogs chylothorax

Question 32

In patients experiencing an Addisonian crisis, fluid therapy is the single most important treatment for an acute crisis. Which fluid type is generally recommended?

Answer 32

0.9% NaCl - contains more NaCl and less K than other crystalloids

Question 33

Correcting hyponatremia: -Should not exceed more than _____ within the first 2-3 hours. -Should not exceed more than _____ in the first 24 hours.

Answer 33

1-2mEq/L (1-2mmol/L) 8-12 mEq/L (8-12 mmol/L)

Question 34

Emergency dextrose dose

Answer 34

0.25-0.5 g/kg diluted 1:3

Question 35

_______ can be used in the long-term management of Addison's disease and contains both gluco- and mineralocorticoids.

Answer 35

Fludricortisone

Question 36

What is the ideal Na/K ratio when monitoring an Addisonian for the long-term?

Answer 36

30-32, no lower than 28 no higher than 32