Hyperadrenocorticism

Front 1

Zones of adrenal cortex and what they secrete

Back 1

G-F-R
Zona glomerulosa - aldosterone
Zona fasciulata - cortisol
Zona reticularis - androgens
"Salt, sugar, sex - the deeper it goes the better it gets."

Front 2

Hypothalamus-pituitary-adrenal (HPA) axis

Back 2

Hypothalamus - corticotropin releasing hormone
Pituitary - adrenocorticotropic hormone (negative feedback on CRH)
Adrenals - cortisol (negative feedback on ACTH and CRH

Front 3

PDH v ADH

Back 3

PDH = 80-85%
- microadenoma (<3mm in 50% D at diagnosis (MRI/CT). 5 -10mm in 30-35% (grossly visible))
- macroadenoma >10mm in 10-20% D at Dx.
- adenocarcinoma = extremely uncommon
- pituitary hyperplasia = extremely rare

ADH = 15-20%
- adrenocortical hyperplasia (bilateral hyperplasia gen from excess ACTH (from PDH). Often diffuse and mistaken for adrenal neoplasia.
- adrenal neoplasia. Endocrine histopath hard - norm v hyperplasia v diffuse neoplasia and adenoma v carcinoma.

Front 4

Adenoma size v Carcinoma size for HyperA

Back 4

Adenoma - <75% of dogs normal kidney. 50% partially calcified
Carcinoma - >50-75% of dogs normal kidney. Vascular invasions/local extension are common and help predict malignancy

Front 5

Signalment for Cushings

Back 5

Middle age - old: >6yrs
F (60%)
Small breed (poodle, dasch, terriers, beagles, GSD, labs, Aus shepherd, maltese, spaniel)

Front 6

Hx and CSx for Cushings

Back 6

4 Ps: PUPD, polyphagia, pot belly, panting
Hepatomegaly
Muscle wasting
Cutaneous signs: hyperpigmentation, skin fragility, alopecia, calcinosis cutis.

Less common: poorly controlled DM, excessive bruising, mm weakness, myotonia, facial n paralysis, sudden acquired retinal detachment syndrome (SARDS)

Front 7

PUPD DDx

Back 7

Renal disease - ARF/CRF, pyelonephritis, post obstructive diuresis, renal glucosuria, renal medullary washout
Liver disease - PSS, hepatic insuff
Endocrine: DM, HypoA, HyperA, HyperT, central and renal DI, acromegaly
Drugs: phenobarbital, corticosteroids, diuretics, thyroid supplement
Psychogenic PD
Pyometra

Front 8

PUPD and polyphagia DDx

Back 8

HyperA
DM - wt loss
HyperT - cats, wt loss
Acromegaly - rare, poorly controlled diabetic

Front 9

Alopecia and hyperpigmentation DDx

Back 9

HyperA
HypoT
FAD, atopy, food allergy
Fungal disease
Demodicosis
Pyoderma

Front 10

Biochem panel for Cushings

Back 10

1. Increased ALP (90-95% cases) - cholestasis and corticosteroid isoenzyme
2. Mild incr ALT and AST
3. Incr cholestrol and triglycerides (90% cases) - glucocort stim of lipolysis
4. Decreased urea - diuresis
5. Elevated BG - GC increase hepatic gluconeogenesis and is an insulin antagonist --> insulin resistance. Occ concurrent DM
6. Stress leukogram
7. Thrombocytosis

Front 11

U/A

Back 11

U/A - dilute <1015-1020. Proteinuria (so check BP). UTI (40-50% cases) dt immsupp, urine retention and lack of protection of concentrated urine. Culture all dogs

Front 12

ACTH stimulation test

Back 12

ACTH stim - blood cortisol emasured at t=0 and t=1
Pre ACTH (cosyntropin) - 0.5-6.0ug/dL
Post - 6-17ug/dL
If post >22ug/dL = Cushings
Simple, quick (decr hospital stress), good spec and sens but $$$

Front 13

LDDST

Back 13

0.01mg.kg dex IV. Cortisol measured at 0 (before dex), 4, 8hrs.
-ve feedback on CRH and ACTH in norm dog = PDH
Loss of normal -ve feedbag but still some response = ADH
Cheap, good sens and spec, can sometimes differentiate btwn PDH and ADH (can also US, HDDST (unreliable), ACTH levels (assay only done in US), CT). But long test (4 and 8hrs) - hospital stress.

Front 14

Urine cortisol creatinine ratio

Back 14

Low spec, high sens - good for ruling out Cushings.
Collect urine at home for 3d. If average UCC in norm range (<35) Cushings ruled out

Front 15

Tx for Cushings - Mitotane
Dose, monitoring (for what and how), maintenance, MOA, side effects, in ADH

Back 15

Mitotane = Lysodren. 50mg/kg/d for 2-10d. Stop if signs of decr appetite. Re-evaluate w ACTH stimulation test (goal is pre and post between 1-5ug/dL)
Maintenance is 50mg/kg/wk. Relapse occurs will have to repeat induction.
Acts by shrinking adrenal cortex (other zones unaffected
Dispense pred for owner to have on hand just in case (0.1-0.2mg/kg/d). Call e3d.
Monitor for change in CSx or if vom/diarr (do ACTH stim). If no end point noted in 7-10d - do ACTH stim then 50mg/kg/d for 5-7d more (up to 75-80mg/kg/d if ADH)
Side effects: anorex, vom, bloody diarrhoea, CNS tox, lethargy, weakness/ataxia, hepatotox, hypoA, bone marrow necrosis.
In ADH: 50% may take 2wks to induce (up to 30-60d), use low dose pred during induction +/- mineralcort during induction.
Monitor w ACTH stim twice yearly but every 3-4mths in first year then every 6mths when stable.
Px: 80-90% achieve remission. 50% relapse and need re-induction. MST 2-2.5y.

Front 16

Tx for Cushings - Trilostane
Dose, MOA, risks, monitor, Px

Back 16

Trilostane = Vetoryl 3-5mg/kg/q12hr. Replaced Lysodren these days. HypoA crisis can occur but ok once taken of Trilostane for 12-24hrs.
Monitor w ACTH stim 2wk, 4wk after initiating Tx. Then e3-4mths during 1st yr. Then e6mths. Test 4-6hr after Trilostane.
Acts by inhibiting steroid-dehydrogenase i.e. steroid synthesis
Px: 60-70% achieve remission. MST 2-2.5y

Front 17

Tx for Cushings - Ketaconazole

Back 17

Acts by inhibiting steroid synthesis via P450 enzyme. Expensive. Hepatotox. GIT signs
Px: 75% respond. Works well w PDH and ADH. Liver toxicity a concern (y of Tx)

Front 18

Adrenal Sx - preop treatment, why preop, periop treatment, Px

Back 18

Pre-op chemo w Trilostane and ketoconazole. Decreases risks of Sx in partic thromboembolism. Lysodren to shrink large tumours
Mineralocorticoids and glucocorticoids periop. Steroids tapered over 2-3wks (takes a while for other adrenal to kick in).
Px: 20-30% do not survive Sx (2wks). Benign gen cured. Malignant ADH gen die in 2-2.5y dt mets.