canine hyperadrenocorticism

Question 1

adrenal gland anatomy - zones and what they produce

Answer 1

• zona glomerulosa: mineralcorticoids (regulate mineral balance) eg. aldosterone
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• zona fasciculata: glucocorticoids (regulate glucose metabolism) eg. cortisol, corticosterone, cortisone
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• zona reticularis: androgens (stimulate masculinization) eg. dehydroepiandrosterone
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• adrenal medulla: stress hormones (stimulate sympathetic ANS) eg. epinephrine, norepinephrine

Question 2

regulation of cortisol secretion

Answer 2

stressors (hypoglycemia, hypotension, fever, trauma, surgery…) act on the hypothalamus > releases CRH, which acts in the pituitary causing the release of ACTH, which act on the adrenals to produce cortisol
> cortisol sends negative feedback to the pituitary and the hypothalamus
> AVP cytokines can also act on the pituitary causing the release of AVP

Question 3

effects of cortisol on the cardiovascular system

Answer 3

• increase myocardial contractility
• increase cardiac output
• increase catecholamine pressor effect

Question 4

effects of cortisol on the metabolism

Answer 4

• increase gluconeogenesis
• increase glycogenolysis
• increase proteolysis
• increase lipolysis

Question 5

Hyperadrenocorticism: Clinical Features
- most common clinical signs
- less common
- uncommon

Answer 5

MOST COMMON:
* Polyuria
* Polydipsia
* Polyphagia
* Excessive panting
* Thin hair coat
* Abdominal distention
* Hepatomegaly
* Muscle weakness
* Systemic hypertension
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LESS COMMON:
* Hyperpigmentation
* Thin skin
* Comedones
* Poor hair regrowth
* Urine leakage
* Recurrent infections
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UNCOMMON:
* Neurological abnormalities
* Myopathy
* Thromboembolism
* GI ulceration / bleeding

Question 6

Hyperadrenocorticism: Common Laboratory Findings for CBC

Answer 6

• Neutrophilia
• Lymphopenia
• Thrombocytosis
• Mild erythrocytosis

Question 7

Hyperadrenocorticism: Common Laboratory Findings fro serum biochem

Answer 7

• Increased ALP
• Increased ALT
  > (ALP > ALT)
• High cholesterol
• High triglycerides
• Mild hyperglycemia

Question 8

Hyperadrenocorticism: Common Laboratory Findings for urinalysis

Answer 8

• USG <1.020
• Proteinuria
• Possibly indications of UTI

Question 9

types of hyperadrenocorticism and how common they are

Answer 9

◦ ~85% pituitary dependent (PDH)
◦ ~15% adrenal dependent
(functional adrenal tumour; ADH)

Question 10

usual signalment for hyperadrenocorticism

Answer 10

◦ Average age 9-11 years
◦ Predisposed breeds:
> PDH: Poodles, Dachshunds, terriers, etc
> ADH: Poodles, Dachshunds, Labs, GSD, terriers
◦ 75% PDH cases <20 kg

Question 11

Diagnostic Goals: HAC

Answer 11

1. Diagnose HAC
   *Screening tests
2. Differentiate PDH from ADH
   *Differentiating tests
3. Detect concurrent diseases, consequences of HAC
   *Basic +/- advanced labwork
   *Imaging

Question 12

Screening Tests for HAC: Options, what negative results mean

Answer 12

1. Urine cortisol to creatinine ratio
2. ACTH stimulation test
3. Low dose dexamethasone suppression test
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   Negative test result has good likelihood of being a true negative

Question 13

Urine Cortisol to Creatinine Ratio test characteritics
- sp, sn, sample, result

Answer 13

• Very sensitivity (~100% sensitive)
• Poor specificity
• Urine collected at home = best sample
• Normal ratio = rule out hyperadrenocorticism

Question 14

Low dose dexamethasone suppression test - is this a good test for HAC? sn, sp

Answer 14

Gold standard screening tool
- Sn ~95%
- Sp 44-73%

Question 15

Low dose dexamethasone suppression test
- how to differentiate normal dog, from PDH vs ADH?
- how do we diagnose?

Answer 15

Normal dog:
◦ Dexamethasone causes negative feedback on pituitary
◦ ↓ ACTH production
◦ Therefore ↓ cortisol
◦ For ~48h
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PDH dog:
◦ Usually transient ↓ in ACTH (and cortisol) production
◦ Variable, only a few hours
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ADH:
◦ Cortisol secretion from tumour independent of ACTH, no effect
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To diagnose HAC, look at the 8 hour cortisol level
* Usually <40 nmol/L in normal dogs
* Usually >40 nmol/L in dogs with HAC

Question 16

Should you do a LDDST or an ACTH stim?

Answer 16

Practicalities
* ACTH availability
* Duration of test
* ACTH not as sensitive
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Non-adrenal illness: false + LDDST
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Diagnose (& differentiate?) etiology with LDDST
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Sometimes need to do both

Question 17

ACTH stimulation test - how it works, sn, sp, how to dx

Answer 17

◦ Cortisol increases after ACTH given
◦ Dogs with HAC will have an exaggerated response to ACTH versus normal dog
◦ Sensitivity, specificity ~80%
◦ Measure serum cortisol before & 1 or 2 h after ACTH

Question 18

Differentiating PDH and ADH with LDDST Results

Answer 18

Suppression of cortisol diagnostic of PDH one or more of:
* 4 hour cortisol <40 nmol/L
* 4 hour cortisol <50% of baseline cortisol (0 hour)
* 8 hour cortisol <50% of the baseline
> But still >40 nmol/L

Question 19

mechanism of pituitary dependent hyperadrenocorticism

Answer 19

• failure of negative feedback
  > anterior pituitary produces a ton of ACTH, which stimulates the adrenals to release a lot of cortisol
  > normally, ACTH and cortisol would act on the hypothalamus to stop it from releasing CRH (which stimulates the AP the release ACTH), and cortisol would also inhibit the release of ACTH from the AP > but in PDH these negative feedback loops are broken, and ACTH is continuously released from the AP despite high ACTH and cortisol levels

Question 20

LDDST
0 hours 150 nmol/L
4 hours 90 nmol/L
8 hours 80 nmol/L
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◦ Can we diagnose HAC? why?
◦ Can we differentiate PDH from ADH?

Answer 20

Can we diagnose HAC?
◦ Yes, 8-hour level is elevated
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Can we differentiate PDH from ADH?
◦ No, have not met one of the suppression criteria

Question 21

Differentiating Tests for PDH vs ADH

Answer 21

1. LDDST
2. HDDST
3. Endogenous ACTH levels
4. Ultrasound

Question 22

HDDST test - how do we do it, what does it tell us?

Answer 22

◦ Giving 0.1 mg/kg dexamethasone
◦ Will suppress cortisol levels in normal dogs at 4 and 8 hours
◦ Some PDH dogs will also have suppression of cortisol levels at 4 and 8 hours when given this higher dose of dexamethasone
> If cortisol suppresses on the HDDST after diagnosing HAC on another test, likely PDH
◦ ADH dogs won’t suppress

Question 23

Abdominal Imaging to differentiate PDH from ADH

Answer 23

Abdominal Ultrasound
* Symmetrical adrenal glands – PDH
* ADH: usually 1 enlarged gland, 1 atrophied gland
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Abdominal Radiographs > Poor sensitivity

Question 24

endogenous ACTH levels to differentiate PDH vs ADH

Answer 24

PDH - ACTH levels are high
ADH - ACTH levels are low