Cushings Flashcards
What is the specificity of the LDDST for cushings?
44% to 73%
How does the severity of non-cushingoid illness affect the likelihood of a false positive test result for cushings?
more severe the nonadrenal illness present, the more likely a false-positive test result for HAC
How sensitive is the LDDST for cushings?
95%
What is occult HAC?
Dogs with occult HAC allegedly have clinical signs and/or routine laboratory abnormalities consistent with classic HAC but have normal serum cortisol concentrations on LDDST and/or ACTH stimulation tests. Alopecia X has been used to describe dogs with occult HAC with dermatologic changes only, mainly bilaterally symmetric alopecia and hyperpigmentation with a puppy coat.
This is now contested
What breeds often have ‘alopecia X’
Poms and chow chows
How do you test for occult HAC?
The syndrome is diagnosed by an ACTH stimulation test with measurement of serum sex hormones (ie, androstenedione, estradiol, progesterone, and 17-hydroxy-progesterone [17OHP]) and aldosterone concentrations pre- and post-ACTH.
What is considered a good way of monitoring HAC tx?
Ideally pre-pill cortisol, with monitoring of electrolytes.
What are possible c/s of cushings?
Polydipsia Lethargy Thromboembolism
Polyuria Hyperpigmentation Ligament rupture
Polyphagia Comedones Facial nerve palsy
Panting Thin skin Pseudomyotonia
Abdominal distention Poor hair regrowth Testicular atrophy
Endocrine alopecia Urine leakage Persistent anestrus
Hepatomegaly Insulin‐resistant diabetes mellitus
Muscle weakness
Systemic hypertension
What are the possible blood abnormalities of HAC?
Neutrophilic leukocytosis Increased alkaline phosphatase Specific gravity ≤1.018–1.020 Lymphopenia Increased alanine aminotransferase Proteinuria Eosinopenia Hypercholesterolemia Indicators of urinary tract infection Thrombocytosis Hypertriglyceridemia Mild erythrocytosis Hyperglycemia
Outline pituitary macrotumour syndrome
Clinical manifestations may develop secondary to mass‐occupying effects of a pituitary or adrenal tumor (AT). A large pituitary tumor may cause neurologic signs (pituitary macrotumor syndrome), including inappetence, anorexia, stupor, circling, aimless wandering, pacing, ataxia, and behavioral alterations.
How can adrenal U/S help your dx of HAC
enlarged adrenal(s) supports this, but normal sized once does not rule it out
What are the indicators to test for HAC
Compatible history and physical examination findings. The greater the number of findings, the stronger the suspicion. Biochemical panel, CBC, urinalysis, and urine protein : creatinine ratio results and blood pressure measurement by themselves are not indications to test.
A pituitary macrotumor.
A diabetic dog with persistently poor response to high dosages of insulin not attributed to another cause, including owner issues.
An adrenal mass.
Persistent hypertension (controversial)
Which drug mimics HAC?
Phenobarb
When is ACTH stim test better than the normally preferred LDDST?
When dx iatrogenic HAC
Outline the principles of the LDDST
In normal dogs, dexamethasone administration causes rapid and prolonged suppression of cortisol secretion. In patients with an AT, dexamethasone at any dosage does not suppress cortisol secretion. In dogs with PDH, ACTH secretion is not appropriately suppressed by administration of a low dose of dexamethasone (0.01 mg/kg), but in 75% of dogs with PDH, cortisol concentrations decrease after administration of 0.1 mg/kg dexamethasone used in the high‐dose dexamethasone suppression test. The other 25% of dogs with PDH do not demonstrate suppression even after receiving higher dexamethasone dosages.35 In dogs with PDH that do not suppress, a large pituitary tumor is more likely
If there is no suppression on a LDDST, what should you do?
Ideally abdo us
How cn you try to determine if an adrenal tumour is malignant?
Possible metastases may be identified by thoracic radiography and abdominal ultrasonography. Metastasis can be confirmed by ultrasound‐guided biopsy. Adrenal gland width >4 cm is highly correlated with malignancy. Invasion into the vena cava or adjacent tissues can be detected by ultrasonography, but CT92 and MRI are more sensitive techniques to identify vascular invasion and detect metastases. Therefore, abdominal ultrasonography ideally should be followed by CT or MRI before adrenalectomy. Differentiating benign from malignant AT often is difficult, even with histopathological examination
Outline -ve feedback in the cortisol pathywa
cortisol has -ve feedback on pituitary and hypothalamus
ACTH -ve on pituitary
What is the most common type of cushings?
PDH - 80%
mostly microadenomas, can get macro
more common in small dogs
Adrenals are 50:50 benign and malignant
What are the most common clinical signs
PUPD - 90%
Polyphagia - 10%
What are the typical cutaneous signs?
Alopecia (not head or feet) Comedones Thin elastic skin Poor wound healing Calcinosis cutis
What can you expect to see on UA
Low SG - if not low consider if this is cushings
Possibl UTI +/- inflammatory response
Poss proteinuria
Poss glucose uria
What are the main biochem changes possible?
ALP - can be massive increase - steroid induction ALT - less increase - hepatocyte damage high cholesterol - lipolysis high glucose - insulin resistance low urea - PUPD high lipase - steroid induction low TT4 - suppression
What should you do if ALT > ALP
Ix for actual hepatopathy
How can rads aid diagnosis?
50% adrenal tumours calcified
Thorax - detection of mets/ possible bronchial calcification
What tests can be performed to test for cushings?
Urine cortisol creatinine ratio
LDDST
ACTH stim
Outline the creatinine cortisol ratio
3 samples from 3 days
Low rules it out
High can be caused by stress
What are the pros of the ACTH stim test
Faster Lss influenced by stress Rules out iatrogenic Detects 85% PDH but only 50% ADH 2 samples Pre tx baseline info given
What are the pros of the LDDST?
90-95% PDH
100% ADH
What will you see with cushings with ACTH stim test?
exagerated response
Iatrogenic - no response at all
Even if +ve, ensure C/S, PE, clin path all fit as other things can cause a +ve
What will you see with cushings with a LDDST?
8 hr sample - if high = HAC
3 hour sample - if low - PDH, high, ADH
How do you discriminate between ADH and PDH?
Adrenal u/s - user dependent, can get incidental tumours, sopme overlap between normal and hyperplastic
HDDST - less acurate than other options, higher dose should suppress PDH but not ADH, doesn;t work in 25% of PDH cases
Endogenous ACTH estimation - in PDH should be high/ normal, in ADH should be low
What are the Tx options for cushings?
Trilostane = licensed
Mitotane (rarely used now)
Sx for tumours (adrenalectomy), bilateral just for control, hypophysectomy
Outline the use of trilostane
Expensive Steroid synthesis inhibitor Short duration - reversible PDH and ADH Best given with food Metabolised by liver, excreted by kidney NEVER SPLIT TABLETS Prevents excess cortisol, sex hormones, aldosterone
How do you monitor trilostane tx?
C/S - thirst, appetite
Check at days 10, 1m, 3m, 6m
Pre pill cortisol testing or ACTH stim, +/- haem, biochem, lytes
When can you not use the pre pill cortisol test?
Stressed, aggressive, sick, oversuppressed animals
In these animals have to do ACTH stim
How do you assess your values with the pre pill cortisol test?
<50 - stop trilostane for 7 days, repeat, if OK, then re-start at a lower dose
50-200 suggests good control. If animal still showing signs then do a cortisol just before due dose. if higher, consider BID dosing
>200 - increase dose
When do you do BID dosing of trilostane?
If c/s controlled part of the day
high ACTH stim
What are the possible s/e of trilostane?
Sudden death iatrogenic addisons unmasking renal dz Neuro signs from macro adenoma become apparent due to the loss of the AI steroid effects Arthritis Atopy
What are possible complications of HAC?
UTI pulmonary thromboembolism Ca calculi Diabetes High BP delayed wound healing
What is corticosteroid withdrawl syndrome?
Occurs in the first 10 days of treatment with trilostane Weakness/ lethargy/ anorexia stiff gait nausea low BG low BP D/t sudden withdrawl of steroids No lyte abnormalities/ ACTH issues No absolute deficiency Stop Tx for 7 days then re introduce at a lower dose.
When is adrenalectomy used?
For adrenal tumours - must do good mets search first
V hard sx, have to deal with complications such as porr wound healing, thrombos, immunosuppression,
13-30% perioperative mortality
How can you treat a pituitary macroadenoma/
Can do radiotherapy
better results if done before onset of clinical neuro signs
Normally still need vetoryl
Or hypophysectomy
Which cushings has worse prognosis?
ADH
