22 – Adrenal and Pituitary Glands

Question 1

Hypothalamic-pituitary-adrenal axis

Answer 1

• Important to maintain basal homeostasis and stress response
  o Circadian rhythm and stress result in CRF (corticotropin releasing factor=CRH) released from hypothalamus
• Cortisol exerts negative feedback on the pituitary and hypothalamus

Question 2

Cortisol measurement

Answer 2

• Stable in most body fluids (usually evaluated on serum)
  o Do NOT use serum separator tubes
• Most steroid medications will CROSS-react with assay
  o Might increase cortisol concentration
  o Exception: DEXAMETHASON
• Most useful to compare baseline concentration an evocative (before and after) test
  o ACTH stim test or LDDST
  o Baseline cortisol alone not as useful (may fluctuate throughout the day)

Question 3

Canine hyperadrenocorticism (HAC)

Answer 3

• Cushing’s disease
  o Pot belly appearance
• Naturally occurring
  o 85% pituitary tumors (usually microadenomas)
  o 15% adrenal tumors (50:50 adenomas:adenocarcinomas)
• Iatrogenic
  o Exogenous corticosteroids (usually high dose or long term)

Question 4

What are the common lab findings with canine hyperadrenocorticism?

Answer 4

• Stress lymphopenia +/- stress leukogram
• Mild erythrocytosis (occasional)
• Mild fasting hyperglycemia
• Increased hepatic enzymes (**ALP, GGT, ALT, GLDH)
  o Combination of steroid induction and glucocorticoid hepatopathy
• Fasting hypercholesterolemia and hypertriglyceridemia
• PU/PD leads to poorly concentrated urine (USG <1.020)
  o Mild proteinuria common
  o Occult UTI in 40-50% of dogs (not much or no inflammation seen with it)

Question 5

Feline hyperadrenocorticism

Answer 5

• Rare, typically older cats (>10y)
• Pituitary dependent hyperadrenocorticism (PDH) more common than adrenal dependent (ADH)
• Most cats have concurrent DMs with poor response to diabetic therapy (difficult to regulate)
• 1/3 of cats will have extreme skin fragility with iatrogenic tearing during routine procedures
• Infections of skin, urinary, respiratory and GI tract are common secondary to cortisol induced immunosuppression

Question 6

ACTH stimulation test (for adrenal function testing)

Answer 6

• DOGS (not recommended in cats)
• Cortisol measured before and 1h after exogenous ACTH
  o Normal: increase in cortisol is expected
  o Spontaneous hyperadrenocorticism: excessive cortisol response is seen

Question 7

What are the indications for an ACTH stimulation test?

Answer 7

• Gold standard to confirm a diagnosis of hypoadrenocortism
• Supports a diagnosis naturally occurring hyperadrenocorticism and monitor a response to therapy
• Confirm a diagnosis of iatrogenic HAC

Question 8

What is iatrogenic hyperadrenocorticism?

Answer 8

• Clinical signs of Cushing’s in a patient with a history of steroid therapy
• Administration of exogenous steroids may cause adrenal ATROPHY and DECREASED ENDOGENOUS cortisol production

Question 9

What do you expect with an ACTH stim test with iatrogenic hyperadrenocorticism?

Answer 9

• Post ACTH-stim cortisol could be LOW or LOW-NORMAL, but typically shows little change from baseline concentration

Question 10

What are the limitations of ACTH stim testing?

Answer 10

• Exogenous ACTH is expensive
• Lower sensitivity than LDDST for diagnosis of naturally-occurring hyperadrenocorticism in dogs
• ACTH not recommended in cats
• Exaggerated response may be seen with chronic illness and stress
• Blunted response may be seen with ketoconazole and prior glucocorticoids
• Does NOT differentiate b/w primary and secondary hypoadrenocorticism or pituitary and adrenal dependent hyperadrenocorticism

Question 11

Low dose dexamethasone suppression test (LDDST) (for adrenal function testing)

Answer 11

• CATS and dogs
• Cortisol measured at baseline then at 3-4hrs and 8hrs after dex
  o Normal: decreased cortisol is expected as dex inhibits ACTH release (8hr used as reference point to evaluate degree of suppression)
  o Hyperadrenocorticsm: lack adequate cortisol suppression at 8hr max (ELEVATED cortisol)
• **first look at 8hr then look to see if there is an escape pattern

Question 12

What are the indications to do a LDDST?

Answer 12

• Preferred screening test for naturally-occurring hyperadrenocorticism
• May help differentiate pituitary from adrenal hyperadrenocorticism

Question 13

If you confirm hyperadrenocorticism with an LDDST, then what do you need to look for?

Answer 13

• 75% of dogs with pituitary dependent hyperadrenocorticism will show an “escape pattern”
  o Cortisol <50% of baseline at either 3-4hr or 8hr
  o Cortisol <40nmol/L at 3-4hr
• Lack of escape pattern=could be either pituitary dependent ADH or ADH
  o Additional differentiating tests include HDDST, endogenous ACTH, imaging

Question 14

What are the limitations of LDDST?

Answer 14

• Equivocal results are possible
• Abnormal test results may be seen with chronic illness and stress
  o Only use in patients with supportive clinical signs and Clinpath findings
  o Delay testing until illness is resolved (or stable/well managed)
• Cannot be used to ID iatrogenic HAC

Question 15

High dose dexamethasone suppression test (HDDST)

Answer 15

• Used to differentiate PDH from ADH in patients with previously confirmed HAC (have NOT yet received treatment)
• Performed the same as LDDST expect with higher dose of dex
• 75% of dogs with PDH will show suppression defined as
  o Cortisol <50% of baseline at 4hr or 8hr
  o Cortisol <40nmol/L at 4hr or 8hr
  o NOT looking for an escape pattern
• Failure to show suppression: may indicate either PDH or ADH

Question 16

Endogenous ACTH concentration

Answer 16

• *HORSES, cats and dogs
• Only available at specialized referral labs
  o Very strict sampling (ACTH is very labile)
• Used for differentiation (NOT diagnosis) of HAC in dogs/cats
  o Increased ACTH with PDH
  o Decreased ACTH with ADH
• Used for diagnosis of PPID in horses

Question 17

Urine cortisol to creatinine ration (UC:CR)

Answer 17

• Dogs and cats
• Cortisol is measured relative to creatine to help account for variations in urine concentration
• Used as a screening test for HAC but GREATLY LACKS SPECIFICTY

Question 18

UC:CR ‘results’

Answer 18

• Elevated=may be seen with HAC, but only other diseases/stress
• If within normal range=can help rule out HAC
• Do NOT use it to confirm diagnosis of HAC (need an ACTH stim or LDDST)

Question 19

Equine metabolic syndrome (EMS)

Answer 19

• Presence of insulin dysregulation +/- obesity, regional adiposity, weight loss resistance, dyslipidemia
• Reflects interaction b/w genetics and environment
• Clinical consequences=INCREASED RISK OF LAMINITIS
• Tend to be younger horses (<15y at onset)

Question 20

PPID

Answer 20

• Hyperplasia or adenoma of pars intermedia of pituitary (loss of inhibition from the hypothalamus)
• Common in age horses and ponies (>15y)
• Clinical signs reflect compression of hypothalamus and cortisol excess
  o PU/PD, muscle atrophy, hyperhidrosis, long hair coat
• Significant portion have concurrent EMS
  o Hyperinsulinemia and/or insulin resistance

Question 21

What are the lab abnormalities that are rarely present with PPID?

Answer 21

• Fasting hyperglycemia and glucosuria
• Hypertriglyceridemia
• Elevated hepatic enzymes
• High FEC

Question 22

What is the goal with PPID/EMS?

Answer 22

• ID horses with them early, before they develop severe disease
• Seasonal and geographical differences
• Lots of grey/equivocal area in interpretation
• Dynamic testing often required
• May have pragmatic limitations (ex. financial or client concerns)

Question 23

What are the recommendations for testing moderation to advanced PPID?

Answer 23

• Resting ACTH concentration
  o High=positive
  o *seasonal increase in ACTH during fall (mid-July to mid-Sept): might be 2x or more URL

Question 24

What are the recommendations for testing early PPID or equivocal resting ACTH results (PPID)?

Answer 24

• TRH stim test
  o Normal=cells do not response to TRH
  o If PPID=cells respond to TRH and ACTH spikes briefly
  o Do this from Jan-June

Question 25

What is recommend to test in all cases of PPID?

Answer 25

- Assessment for possible insulin dysregulation o RESTING insulin concentration

Question 26

What are the recommendations for testing for EMS?

Answer 26

- Resting insulin concentration o *Use only for convenience or monitoring o ONLY ID more severely affected animals (Low sensitivity/high specificity) o Fasting sample NOT recommended but restrict access to grain for at least 4hrs o Positive result=hyperinsulinemia (DDx: PPID, pregnancy, stress, illness, high energy forage) o Evidence of seasonal variation with high insulin in winter months - Dynamic testing o Oral sugar test

Question 27

Oral sugar test for EMS

Answer 27

- Assessment of post-prandial insulin response - Requires fasting for 3-6hrs - Administer corn syrup orally o Collect blood at 60 and/or 90min o Measure insulin and glucose