Untitled

A case based approach to PD/PU
should I ever perform a water

deprivation test...?
Mark Dunning
School of Veterinary Medicine and Science
So how does all this fit

together?
Case 1
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
Rectal examination revealed the prostate to be within normal

limits
Case 1
Primary problems
PD/PU
Polyphagia
Secondary problems
Heart murmur
Bed wetting
Case 1
Differentials for PD/PU:
given this signalment and history is most likely to

reflect polyuria with compensatory polydipsia:
loss of medullary concentrating gradient (hypoadrenocorticism,

CKD, liver disease)
hypercalcaemia (toxicosis, neoplasia, endocrinopathies, parasites
granulomatous disease)
infection
endocrinopathies (hyper/hypothyroidism, hyperadrenocorticism,
DM)
hypokalaemia
primary renal glycosuria/tubular disorders
Cardiac disease
drug therapy
central/primary nephrogenic diabetes insipidus
primary polydipsia with compensatory polyuria:

psychogenic polydipsia or
CNS lesions
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
Epithelial cells, WBC, bacteria
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
Bile acids (fasting)
12*
Bile acids (post-feeding)

(0-10)
27 *
(0-5)
Is this a significant finding?

Not on its own!
So what about adrenal function then?
ACTH stim results within normal limits
No suggestion of hyper or hypo adrenocorticism
Case 1
CBC unremarkable
Hmmmm
remember a negative result IS helpful!
Case 1
Biochemistry, CBC and functional testing do not identify the

primary underlying cause of the PD/PU
Significant functional liver and adrenal

disease do not seem to be present
So what next in terms of investigations?
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
Paired osmolality measurements

Urine
276mOsm/kg
Serum
299mOsm/kg
(280-310)
SO EVIDENCE THAT KIDNEYS CAN PRODUCE DILUTE URINE
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
You still havent got the urine cultures back
Abdominal ultrasound
Liver moderately large and hyperechoic

Normal prostatic size, one large cyst 1.5cm diam, one small cyst
Adrenals NAD
Kidneys NAD
Bladder NAD
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
Inulin clearance result

97.1ml/min/m2
(83.5-144.3ml/min/m2)
(60.2-96.3 CRD)
(50.0-76.2 CRD+PU/PD)
Case 1
So to summarise
No evidence of primary renal disease

No evidence of functional liver disease
No evidence of current hyperadrenocorticism
No evidence of neoplasia
BUT suspicion of UTI and prostatic abnormalities
So where next then..
Cultures have now arrived!

Profuse mixed growth
E Coli
-Haemolytic strep
Both sensitive to marbofloxacin and cephalexin

So what do you think of this result and would you treat this
I would treat but
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
A number of possibilities are less likely at this point:

Compensated CKD unlikely given GFR results
Liver disease possible but very early given the mild bile
acid increase
Cardiac disease given the heart murmur
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
Aspirate of fluid revealed growth of similar E Coli with same

sensitivity profile
Further antibiotics provided for 8 weeks
(Prostatic abscessation has been reported as cause of PD/
PU)
Maybe mild change in PD/PU but not much
Ultrasound perhaps showed some progresison in the

degree of cystic change.
But adrenals plump and liver slightly hyperechoic..
SO. THE SURGEONS GOT INVOLVED.!
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
now however owner reports some changes in the hair

coat..
What next then??
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)
CBC remains unremarkable

Urine
USG
1.005
(prev 1.008)
UPC
0.67
(prev 0.18)
Bacteria on sediment.
Case 1
ACTH stimulation test
Cortisol pre
post
17-OHP
83nmol/l
528nmol/l
pre
<0.1nmol/l
post
10.3nmol/l
So how significant is all this now then.............

In addition to this further UTI identified following cessation of
antbiotics.
Case 1
Further course of antibiotics + addition of cranberry extract
So possibilities for further investigations to aid with confirmation
Cranberry extract 11mg/kg PO BID (Cranactin suitable formulation)
Further HAC testing ACTH assay

Liver biopsies
Pituitary imaging
This case is currently ongoing and highlights the complex interactions

between organ systems
No clear primary condition is noted given the testing performed
Possible HAC (and secondary UTI)
Possible grumbling liver disease (and secondary UTI)
Possible chronic susceptibility to UTI with partial DI
Thus all this still requires further investigations to determine OR non-specific

treatment trials
Importantly ADH, when administered, will increase USG if endogenous secretion isnt
maximal
Ultimately this is a very expensive condition to investigate AND to

provide the owners with black and white answers as here it
remains very grey..
Case 2
Signalment
6yo, FN, English Setter
History
6 months progressive PD/PU

Polyphagia
Urinary incontinence (noted for past 18 months)
Lethargy/exercise intolerance
Haircoat lost its sheen
Case 2
Physical examination findings
Agitated during examination

Overweight
Grade II/VI left systolic heart murmur, no gallop or arrhythmia
Cutaneous mass over left gluteals
non-painful, adherent to underlying tissues
enlarged recently
Case 2
Where does that leave us?
Primary problems:
PD/PU
Polyphagia
Systolic heart murmur
Secondary problems:
Urinary incontinence
Obesity
Haircoat changes
Case 2

CKD, liver disease)
infection
DM)
hypokalaemia
Cardiac disease
drug therapy

CNS lesions
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
Excessive activity/physiological/behavioural (*)
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
IMHA/haemolysis, myopathies, myelo/lymphproliferative neoplasia, exscessive plasma
Glomerular
Hypertension, endocrinopathies, CKD, inflammation/amyloid/infection, immune mediated
Tubular
Defective tubular resorption/secretion (acquired/congenital tubular disease)
Inflammatory
Haemorrhage, infection/inflammation, neoplasia,
So what are the next steps in this case?

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
Bile acids (fasting)
<0.5
0-5
Bile acids (postfeeding)
<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
Primary liver disease, cholangiohepatitis/cholangitis

Biliary obstruction
GI disease, pancreatic disease
Endogenous/exogenous glucocorticoids
Mild reduction in urea

Liver disease, diuresis, metabolic disorders, malnutrition
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)
What further tests might we perform at this

point?
Case 2
Any other urine tests of value?
UCCr
10x10-6 (<30)
Suggested as excellent screening test for HAC

This test has a sensitivity of >90%, although some studies
suggest 100%
Specificity however is lower around 85% for values above
60
Important for test in stress free environ
Most appropriately performed at home
So where does that leave us now?

Any further blood samples of value at present?
Case 2
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
Does this help?

Rules it out, which is as we all know a useful piece of info!
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
Diagnostic imaging would be very valuable at this point as no

diagnostic abnormalities as yet
Thoracic radiographs
Case 2
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
Thoracic radiographs unremarkable
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)
Incidentalomas are really those seen when not expected
Case 2
What next then?
Review the adrenal function testing
Low dose dexamethasone suppression
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
Further hormonal analysis

Thyroid analysis
T4
TSH
41nmol/l (13-52)
0.24ng/ml (<0.41)
So no current evidence of endocrinopathy despite adrenal

mass.
Where should we go now?
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)
Does this enable us to reach a diagnosis?

Biopsy would help in reaching that diagnosis
however owners were understandably not willing to risk this
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
If cortisol is not supportive of HAC but 2-3 other

hormones are then a diagnosis of AHAC may be
considered
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
However not invariably the answer as pituitary dependent

disease may also present atypically
Case 2
Atypical hyperadrenocorticism
Therapy
Dogs with pituitary AHAC may respond well to conventional
medical therapy
Trilostane is current licensed treatment for PDH

Melatonin has also been suggested as a treatment for those animals
with sex steroid excess however as yet no published reports on its use
in dogs or cats
Surgical therapy for pituitary AHAC is poorly available

For adrenal dependent disease surgical therapy provides a high
risk option
Important consideration as to the extent of any invasion into the local

BV and also evidence of metastasis
Prognosis for adrenal neolpasia poor as invariably malignant
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
Principle of effect is different to mitotane

Enzymatic inhibition of steroidogenesis
3-hydroxysteroid dehydrogenase
Studies suggest that concentration requirement increases over
time with PDH
Importantly trilostane has shown no advantage over mitotane in
treatment AHAC
Case 2
Monitoring of atypical adrenal gland disease
Cortisol response in this case was difficult to predict
Routinely measure ACTH stim @ 10d, 4 weeks, 3months then

every 3 months
Monitoring has been suggested to be difficult using

alternative adrenal steroids despite their value in
diagnosis
17-OHP has been reported to rise following administration of

enzyme inhibitors (trilostane blocks 3-hydroxysteroid
dehydrogenase)
However its position in the synthesis pathway is after the blockade

Cross reactivity with 17-hydroxy pregnenolone (which occurs
before 3-hydroxysteroid dehydrogenase and so increases
following blockade) is thought to be the reason 17-OHP increases
following inhibition
But in this case it was measured and showed a reduction:
Importantly there is little published data on its production and
measurement in atypical HAC for this to invariably be the case
Case 2
Currently the dog is well receiving trilostane

Clinical signs have predominantly resolved
Owners are happy with current progress
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


CKD, liver disease)
infection
DM)
hypokalaemia
Cardiac disease
drug therapy

CNS lesions
Case 3
Differentials for lymphadenopathy
Hyperplastic/Reactive
Non-neoplastic lymphoid proliferation
Inflammation
Non-lymphoid proliferation (immune mediated/infectious)
Neoplasia
primary/metastatic
Generalised weight loss (increased prominence)
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
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
Major biochemical abnormalities:
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!
Any access to toxins?

Psoriasis creams
Calcium containing vitamin supplements
Vitamin D Rodenticides
Case 3
What would be reasonable tests at this point?
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
Measurement is difficult as variable accuracy

Influenced by many variables
Serum, heparin whole blood or plasma
Need to be collected anaerobically to reduce changes in pH by loss of
CO2 to air
Serum and plasma should be harvested within 1 hour of collection to
reduce errors associated with lactate generation from RBC
Case 3
Ionised calcium
More stable in plasma than whole blood
Do not use silicone separator tubes as gel contains Ca

Serum and plasma ionised iCa is stable in glass tubes for 1
week at 4C and 6 weeks at -20C
iCa in heparinised whole blood is reported to be stable for 9
h at 4C
pH changes affect iCa
Changing pH alters the negative charge on albumin molecules
Increasing pH decreases iCa (more calcium binds to alb)
Lowering pH increases iCa (opposite effect)
iCa changes by ~5% for each 0.1 change in pH
Difficult to assess iCa in animals with acid base dyscrasias

Reporting of adjusted iCa is not necessarily accurate
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?
Importantly no strict cut-off above which treatment should be

initiated
Choice is based on clinical signs in individual patients
Presence of obvious complications
Often quoted Ca x Phosphate product (>60-80 associated with
tissue mineralisation)
This patient needs diuresis to reduce further renal

damage
These cases need intensive diuresis as RIP from renal
complications regardless of underlying cause
Choice of fluids?
Saline as high conc Na leads to increased Ca loss through the kidney as

competes for Na resorption
Calculate volume dehydration and correct either over 6 hours or 24
hours
rates need to be tailored to individual patient
Twice maintenance is NOT intensive diuresis
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
Given as infusion over 24 hours

0.9-1.3mg/kg in dogs
Higher dose in cats 1.5-2.0mg/kg
Side effects include
Nausea, diarrhoea, hypocalcaemia,

hypophosphataemia, hypersensitivity reactions
Zoledronate
Not personally used for HHCM but used as analgesia for

osteosarcoma
Extremely expensive
Very effective, is used yearly in humans with osteoporosis
Case 3
Any further tests at this point?
PTH/PTHrp
PTH
PTHrp
18.0 (18-130)
0.3 (>1.0 suggestive of malignancy)
NB IL-1, various prostanoids, TGF- and TNF- also increase calcium
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
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
Prescapular and submandibular LN
56% of the lymphoid population were medium to large

cells. Monomorphic in appearance with high nuclear to
cytoplasmic ratio and prominent nucleoli. There was a
subjective increase in mitotic figures
Liver
Spleen
NAD
NAD
CMM mass
Moderate proportion of lymphoid cells with large

occassionally cleaved nuclei with an increase in mitoses.
Overall findings suggestive of stage III large cell

lymphoma
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
Modified madison wisconsin protocol chosen
Anecdotally thought protocol which is associated with best remission rates
Hypercalcaemia resolved within 24 hours of starting therapy
This is very important feature with hypercalcaemia secondary to lymphoma
Unfortunately azotaemia persisted despite this there was no significant

progression during the chemotherapy protocol
Remission for 6 months then sadly relapsed
Owners declined further chemo L

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A case based approach to PD/PU

should I ever perform a water

School of Veterinary Medicine and Science

So how does all this fit

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

Rectal examination revealed the prostate to be within normal

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

given this signalment and history is most likely to

loss of medullary concentrating gradient (hypoadrenocorticism,

primary polydipsia with compensatory polyuria:

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

Epithelial cells, WBC, bacteria

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

Bile acids (fasting)

Bile acids (post-feeding)

Is this a significant finding?

School of Veterinary Medicine and Science

Biochemistry, CBC and functional testing do not identify the

Significant functional liver and adrenal

School of Veterinary Medicine and Science

Paired osmolality measurements

School of Veterinary Medicine and Science

You still havent got the urine cultures back

Liver moderately large and hyperechoic

School of Veterinary Medicine and Science

Inulin clearance result

School of Veterinary Medicine and Science

No evidence of primary renal disease

So where next then..

Cultures have now arrived!

Both sensitive to marbofloxacin and cephalexin

School of Veterinary Medicine and Science

A number of possibilities are less likely at this point:

Aspirate of fluid revealed growth of similar E Coli with same

Maybe mild change in PD/PU but not much

Ultrasound perhaps showed some progresison in the

now however owner reports some changes in the hair

School of Veterinary Medicine and Science

CBC remains unremarkable

School of Veterinary Medicine and Science

So how significant is all this now then.............

School of Veterinary Medicine and Science

Further course of antibiotics + addition of cranberry extract

So possibilities for further investigations to aid with confirmation

Cranberry extract 11mg/kg PO BID (Cranactin suitable formulation)

Further HAC testing ACTH assay

This case is currently ongoing and highlights the complex interactions

Thus all this still requires further investigations to determine OR non-specific

Ultimately this is a very expensive condition to investigate AND to

6 months progressive PD/PU

School of Veterinary Medicine and Science

Agitated during examination

School of Veterinary Medicine and Science

School of Veterinary Medicine and Science

given this signalment and history is most likely to