Professional Documents
Culture Documents
Mark Dunning
Very complicated
Case 2
Reasonably complicated
Case 3
Very straightforward
The end
Case 1
11 yo, MN, Border Collie Cross
12 month history of PD/PU
Longer term history of haematuria which resolved following
castration
Occasional wet bed when PD/PU most severe
Since castration has appeared polyphagic
No other abnormalities
Case 1
Clinical examination findings
Oral mucus membranes pink and moist
Peripheral lymph nodes within normal limits
Grade III/VI left basal harsh systolic murmur
Previous ultrasound suggested asymptomatic MVD
Case 1
Primary problems
PD/PU
Polyphagia
Secondary problems
Heart murmur
Bed wetting
Case 1
Differentials for PD/PU:
Case 1
Differentials for polyphagia
Hyper/hypoglycaemia *
Hyperadrenocorticism *
Hyperthyroidism *
Pancreatic disease
Malabsorptive/maldigestive syndromes/starvation
HE/PSS *
Drug induced *
Primary polyphagia
Destruction of satiety centre
More palatable diet
Excessive activity/physiological/behavioural
Case 1
What investigations do we want first in this case?
Urinalysis (ALWAYS THE FIRST ONE!)
Biochemistry
CBC
Case 1
Parameter
Value
pH
7.7
Protein
Positive (+)
Glucose
Negative
Ketones
Negative
Urobilinogen
Negative
Bilirubin
Negative
Blood
Negative
Haemoglobin
Negative
USG
1.008
UPC
0.18
Sediment
Culture
pending
Case 1
So what does this tell us?
Hyposth/isosthenuria
Proteinuria
Active sediment
Is that sufficient for a diagnosis in this case?
Case 1
Parameter
Value
Normal range
ALP
208*
0-135
Cholesterol
10.9 *
3.5-7.0
ALT
197 *
0-40
GT
25 *
0-14
Total bilirubin
4.9
0-5.0
Total protein
68.9
55-75
Albumin
33.6
29-35
Globulin
35.3
18-38
Urea
4.0
3.5-7.0
Creatinine
50 *
100-133
Calcium
2.85
2.3-3.0
Phosphate
1.6
0.9-1.6
CK
220
0-400
Glucose
4.8
3.0-5.5
Chloride
110
95-117
Sodium
146.4
135-150
Potassium
4.64
3.5-5.6
Case 1
Abnormalities
ALT (T1/2 = ~3d)
hepatocellular damage (hypoxia, metabolic, neoplasia,
nutritional, inflammation/infection, toxic, trauma, induction
by drugs), muscle damage
ALP (T1/2 = ~3d)
Cholestasis/cholangitis, drug/steroid induced, hormonal
disease, GI disease, bone pathology, breed related (Husky,
Scotty)
GT (T1/2 = ~3d)
Similar differentials for ALP
Cholesterol
Post-prandial, endocrinopathies, familial (Briards, Min
Schnauzers), PLN, pancreatitis, cholestasis
Case 1
Are the liver enzymes significant?
Require a functional test to determine if influencing function
Important that owners understand between inflammation and
function
Sore leg - no leg principle
BAST less prone to error the NH3 and is most commonly used
Case 1
The results of the BAST
12*
27 *
(0-5)
Case 1
CBC unremarkable
Hmmmm
remember a negative result IS helpful!
Case 1
Case 1
Can we therefore obtain more information from
the urine at this point?
Compensated CKD remains an important differential in
this case
FEE will perhaps be of value:
Sodium
0.42% (0.00-0.70)
Potassium
8.8%
(0.0-20.0)
Calcium
0.09% (0.00-0.40)
Phosphate
9.7%
(3.0-39.0)
THUS NO EVIDENCE FOR TUBULAR DYSFUNCTION
Case 1
Further analysis of the abdomen is now essential as urine
concentration is lower than plasma and thus kidneys can
dilute urine
Does this rule out CKD in the absence of obvious tubular
dysfunction?
Not convincingly
Abdominal ultrasound
Case 1
To rule out CKD a GFR study is required
We will be able to assess if the PD/PU represents
compensated CKD or is normal
GFR performed using single injection inulin clearance
method
Rapid injection of inulin
Blood samples (6) obtained over period of 6 hours
(83.5-144.3ml/min/m2)
(60.2-96.3 CRD)
(50.0-76.2 CRD+PU/PD)
Case 1
So to summarise
Case 1
Are we now at a point where we can identify the
cause of the PD/PU?
Various possibilities must still exist in addition to the
lower UTI:
Adrenal gland disease UTI common secondary
complication
Upper UTI possible given the USG value
necessary to induce PD/PU
Case 1
UTI treated for 8 weeks
Urine cultures sterile
BUT no change in PD/PU
Further prostatic ultrasound revealed mild increase in
size of cysts
Case 1
Decided to omentalise the prostate
Biopsies revealed chronic moderate prostatitis
Culture of the tissue was sterile
Thus Successfully managed but still PD/PU
More urine?
Have another look for HAC?
Further liver evaluation?
MWDT?
Case 1
Repeated Biochemistry results:
Salient biochem findings (similar to previously)
ALT
ALP
Cholesterol
219iu/l
281iu/l
12.3mmol/l
(prev 197iu/l)
(prev 208iu/l)
(prev 10.9mmol/l)
Case 1
ACTH stimulation test
Cortisol pre
post
17-OHP
83nmol/l
528nmol/l
pre
<0.1nmol/l
post
10.3nmol/l
Case 1
Importantly ADH, when administered, will increase USG if endogenous secretion isnt
maximal
Case 2
Signalment
6yo, FN, English Setter
History
Case 2
Physical examination findings
Case 2
Where does that leave us?
Primary problems:
PD/PU
Polyphagia
Systolic heart murmur
Secondary problems:
Urinary incontinence
Obesity
Haircoat changes
Case 2
Differentials for PD/PU:
Case 2
Differentials for polyphagia
Hyper/hypoglycaemia *
Hyperadrenocorticism *
Hyperthyroidism
Pancreatic disease (*)
Malabsorptive/maldigestive syndromes/starvation (*)
HE/PSS *
Drug induced
Primary polyphagia (*)
Destruction of satiety centre
More palatable diet
Case 2
Differentials for incontinence
True incontinence
USMI*
Developmental anomalies
Hormonal changes *
Neoplasia (*)
Infection (*)
Overflow phenomena
Dysynergia
Case 2
What are your next steps?
Urine sample (yes the first sample you need!)
Serum biochemistry
CBC
Case 2
Parameter
Value
pH
6.0
Protein
Positive (+)
Glucose
Negative
Ketones
Negative
Urobilinogen
Negative
Bilirubin
Negative
Blood
Negative
Haemoglobin
Negative
USG
1.012
Sediment
Unremarkable
Culture
Sterile
Case 2
Parameters
Value
Urine protein
27mg/dl
Urine creatinine
47mg/dl
UPC
0.57
(<0.2)
Proteinuria
Preglomerular
Glomerular
Tubular
Inflammatory
Case 2
Parameter
Value
Normal range
ALP
148*
0-135
AST
16
0-45
ALT
26
0-40
GT
0-14
Total bilirubin
2.5
0-5.0
Total protein
68
55-75
Albumin
35
29-35
Globulin
28
18-38
Urea
2.6*
3.5-7.0
Creatinine
101
0-130
Calcium
2.91
2.3-3.0
Phosphate
1.1
0.9-1.6
CK
35
0-400
Glucose
4.6
3.0-5.5
<0.5
0-5
<0.5
0-10
Chloride
114
95-117
Sodium
150
135-150
Potassium
4.0
3.5-5.6
Case 2
So where do these results leave us?
Mild increase in ALP
Possible causes of this
Case 2
What would you do at this point
Are we any further at this stage
Unlikely to be HAC on tests so far despite clinical
suggestion
No evidence of hyperglycaemia or glycosuria
Unlikely to be liver disease either clinically or biochemically
Unlikely to be related to hypercalcaemia as not evident on
biochemistry
No historical or biochemical evidence of renal failure (would
also be unlikely given polyphagia)
Case 2
Any other urine tests of value?
UCCr
10x10-6 (<30)
Case 2
ACTH stimulation test
For HAC this is a relatively sensitive test, although its
specificity is somewhat variable
It is reported to identify >85% of pituitary HAC cases
It is considered less prone to influence of non-adrenal
illness than other screening tests
Hormone
Basal
Post
Reference
Cortisol
<20
152
B 28-250
P >660
Case 2
Cross reactivity in lab methods using cortisol as assay
Cortisol
100%
Prednisolone
69%
11-desoxycortisol
7.5%
Prednisone
6.4%
Cortisone
4.2%
Corticosterone
3.5%
Sprinolactone
<0.2%
Dexamethasone
<0.1%
Case 2
Any thoughts attributed to the mass on the gluteals?
Differentials included neoplasia as well as inflammatory/
infectious causes
FNA performed
Benign cyst with keratin deposits
Inflammation around keratin but no evidence of neoplasia
Case 2
Do we want further information in addition to our blood and
urine sampling?
Blood pressure measurement
Upper end of normal: 150mmHg
DDX stress, primary hypertension, CKD, adrenal disease, nephrotic
syndrome, CHF, toxicity
Case 2
Abdominal ultrasound
Liver moderately enlarged, rounded margins,
hyperechoic
Right adrenal small
Left adrenal 2.1cm mass detected in the cranial pole.
Caudal pole also enlarged 9mm and heterogenous.
There appeared to be ingrowth of the mass into the
phrenicoabdominal vein
Case 2
Case 2
How significant is the mass in the adrenal?
Given the clinical signs it is generally considered that
this would be functional
Invasion into blood vessels is considered significant
Bigger the mass more likely significant
Also more likely to have metd (despite negative US and
rads)
Case 2
What next then?
Pre
<20nmol/l
(up to 250)
3 hours post <20nmol/l
(<40nmol/l)
8 hours post <20nmol/l
(<40nmol/l)
This is considered more sensitive as a screening test for HAC than the
ACTH stim (90-95% sensitive).
Specificity however is lower and is influenced by non-adrenal illness
41nmol/l (13-52)
0.24ng/ml (<0.41)
Case 2
Adrenal tumours when functional may produce a
number of steroid hormones and their precursors
Cortisol
Catecholamines
Aldosterone
Oestradiol
Progesterone
Intermediary hormones
17-hydroxyprogesterone
Deoxycorticosterone
Ah ha.
Case 2
Hormone
Basal
Post
Reference
Cortisol
<20
152
B 28-250
P >660
17-OHP
2.1
22
B <3.0
P >10 possible sex
hormone excess
Oestrodiol
80
80
>10 follicular
activity
Aldosterone
<20
96
B <960
P 200-2100
Case 2
Hormone
Basal
Post
Reference
Cortisol
<20
152
B 28-250
P >660
17-OHP
2.1
22
B <3.0
P >10 possible sex
hormone excess
Oestrodiol
80
80
>10 follicular
activity
Aldosterone
<20
96
B <960
P 200-2100
Case 2
Hormone
Basal
Post
Reference
Cortisol
<20
152
B 28-250
P >660
17-OHP
2.1
22
B <3.0
P >10 possible sex
hormone excess
Oestradiol
80
80
>10 follicular
activity
Aldosterone
<20
96
B <960
P 200-2100
Case 2
Hormone
Basal
Post
Reference
Cortisol
<20
152
B 28-250
P >660
17-OHP
2.1
22
B <3.0
P >10 possible sex
hormone excess
Oestradiol
80
80
>10 follicular
activity
Aldosterone
<20
96
B <960
P 200-2100
Case 2
Will anything else be of value?
ACTH assay
<5.0pmol/l (20-80)
Case 2
Atypical hyperadrenocorticism due to functional
adrenal tumour
Uncommon manifestation of adrenal gland neoplasia
Strongly suspected in those animals with overt clinical
signs of HAC with repeatedly normal adrenal functional
testing
In these cases measurement of other adrenal steroids
may be very valuable in diagnosis
CSLS will perform a panel of non-cortisol adrenal enzymes
Reasonable cost to client however
Measurement would be recommended to include
Initially 17-hydroxyprogesterone,
Subsequently: oestradiol, aldosterone, androstenedione,
progesterone and testosterone
Case 2
Why did the initial functional testing show
negative results
No clear answer to this
Possible that the functional activity of the adrenal tumour
blocks cortisol production via feedback at the level of the
adrenal and pituitary
Certainly evidence of suppression of ACTH
Case 2
Atypical hyperadrenocorticism
Therapy
Dogs with pituitary AHAC may respond well to conventional
medical therapy
Case 2
Medical therapy
Trilostane (Vetoryl, modrenal (human))
Still relatively new medication which requires careful
consideration before using
Complications are becoming more frequently recognised
Not, as once suggested, significantly safer than mitotane
Hypoadrenocorticism due to adrenal necrosis
Case 2
Monitoring of atypical adrenal gland disease
Cortisol response in this case was difficult to predict
dehydrogenase)
Case 2
Case 3
4 year old, FN, Boxer
Acute onset PD/PU and anorexia
Case 3
Physical examination findings
Subdued
Moderate clinical dehydration ~5%
Mucus membranes tacky with normal CRT
Prominent S/M, prescap and popliteal LN
Doughy abdomen
Anal sacs within normal limits
Case 3
Problem list
Primary problems
PD/PU
Prominent LN
Secondary problems
Anorexia
Tacky mucus membranes
Subdued
Case 3
Differentials for PD/PU:
Case 3
Differentials for lymphadenopathy
Hyperplastic/Reactive
Non-neoplastic lymphoid proliferation
Inflammation
Non-lymphoid proliferation (immune mediated/infectious)
Neoplasia
primary/metastatic
Case 3
So what next?
Urinalysis
Biochemistry
CBC
Case 3
Parameter
Value
pH
7.0
Protein
Positive (+)
Glucose
Negative
Ketones
Negative
Urobilinogen
Negative
Bilirubin
Negative
Blood
Negative
Haemoglobin
Negative
USG
1.018
UPC
0.2 (<0.2)
Sediment
Unremarkable
Culture
Sterile
School of Veterinary Medicine and Science
Case 3
Parameter
Value
Normal range
ALP
97
0-135
ALT
286*
0-40
GT
0-14
Total bilirubin
3.6
0-5.0
Total protein
64.4
55-75
Albumin
27*
29-35
Globulin
38.4*
18-38
Urea
17.2*
3.5-7.0
Creatinine
223*
0-130
Calcium
4.38*
2.3-3.0
Phosphate
1.44
0.9-1.6
CK
40
0-400
Glucose
3.6
3.0-5.5
Cholesterol
7.0
3.5-7.00
Triglycerides
0.55
0.00-1.00
Chloride
111
95-117
Sodium
150.1
135-150
Potassium
5.08
3.5-5.6
Case 3
CBC
Unremarkable
Azotaemia (mild-moderate)
Hypoalbuminaemia (mild)
Hyperglobulinaemia (mild)
Hypercalcaemia (severe)
Case 3
Differentials for hypercalcaemia:
Hyperparathyroidism (primary/secondary/tertiary)
Hypoadrenocorticism
CKD
Myelo/lymphoproliferative neoplasia
Anal sac adenocarcinoma (+other carcinomas/solid tumours)
Granulomatous disease
Vitamin D toxicity
Angiostrongylosis
Lab error
Age related
Idiopathic (cats)
(Increased bone turnover/metastasis to bone)
Case 3
So on the basis of these differentials.
Any further questions to ask the owner?
When was she last wormed?
Wormed recently with panacur, remarkably enough at the appropriate
concentration and duration to treat lungworm!
Case 3
What would be reasonable tests at this point?
ACTH stimulation test
WNL no evidence of hypo or hyperadrenocorticism
Ionised calcium
2.34mmol/l (1.12-1.40)
Case 3
Ionised calcium
Important as physiologically active fraction
Total hypercalcaemia does NOT mean ionised hypercalcaemia
Case 3
Ionised calcium
Case 3
Hypercalcaemia
Hyperparathyroidism* (primary/secondary/tertiary)
Hypoadrenocorticism (*)
CKD (*)
Myelo/lymphoproliferative neoplasia *
Anal sac adenocarcinoma (+ other carcinomas/solid
tumours) *
Granulomatous disease (*)
Vitamin D toxicity *
Angiostrongylosis
Lab error
Age related
Idiopathic (cats)
(Increased bone turnover/metastasis to bone) (*)
Case 3
Anything you want to do at this stage?
Case 3
Further treatments to control hypercalcaemia
Best treatment is to ID cause and begin specific therapy
But other therapies
Loop diuretics
GC (care before made diagnosis)
L-asparaginase (single dose pricey but important to aid
with diagnosis under certain circumstances)
Bisphosphonates (pamidronate/zolendronate)
Calcitonin (for rapid reduction, not sustained use as
tachyphylaxis seen, can cause hypoCa)
Specific alteration of PTH-signalling pathways
anti-PTHrP Ab trialling in metastatic breast cancer patients
Bisphosphonates
Bisphosphonates inhibit bone resorption without
inhibiting the process of bone mineralization
This results in stabilisation, and even
enhancement, of bone mineral density
Bisphosphonates directly inhibit bone resorption
by binding to hydroxyapatite crystals
Bisphosphonates impede osteoclast activity and
induce osteoclast apoptosis; both mechanisms
result in inhibition of bone resorption
Bisphosphonates
Relative efficacies vary of different drugs
Etidronate
Clodronate
Pamidronate
Alendronate
Zoledronate
1
10
100
1000
10,000
Bisphosphonates
Pamidronate
Zoledronate
Case 3
Any further tests at this point?
PTH/PTHrp
PTH
PTHrp
18.0 (18-130)
0.3 (>1.0 suggestive of malignancy)
So where now??
Does this help to rule out CKD and in neoplasia?
Case 3
How do we approach this case now?
Can we tell whether this is renal or non-renal at this stage?
Difficult from the blood samples obtained so far but would appear
non-renal.
So what do we need to do now to clarify things?
Diagnostic imaging would be helpful
Samples from the lymphoid organs
Case 3
Thoracic radiographs
Interstitial pattern
Suggestion of mediastinal ST opacity
Abdominal ultrasound
Hypoechoic liver
Regular structure
Spleen unremarkable
Mediastinum well defined homogenous hypoechoic mass
~2.3-3.7cm.
Case 3
Case 3
Case 3
What next then?
Aspirates would certainly be a good idea
Case 3
Fine needle aspirates
Liver
Spleen
NAD
NAD
CMM mass
Case 3
Large cell lymphoma (no further typing
performed)
Prognosis variable most optimistic would be 12-18 months but in this case
Negative prognostic indicators
Hypercalcaemic
Unwell (substage b)
Sternal/mediastinal lymphadenopathy