High ALP…Do I Hit The Panic Button Or The Snooze Alarm?
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Transcript High ALP…Do I Hit The Panic Button Or The Snooze Alarm?
High ALP…Do I Hit The Panic
Button Or The Snooze Alarm?
Jason M. Eberhardt, DVM, MS, DACVIM
High ALP – Dazed and confused?
VERY common lab finding
39% of ALL dogs
51% of dogs > 8 yrs old
Often a diagnostic dilemma
For liver disease
High sens. (86%) but…low spec. (49%)
Pathophysiology review
Heterogeneous group of enzymes
Catalyze the hydrolysis of phosphate from organic
compounds in an alkaline pH
Poorly defined biologic functions
Total serum ALP
L-ALP, B-ALP, C-ALP (Dog only)
½ lives of intestinal, kidney and placenta is only minutes
Bone Alkaline Phosphatase
Attached to the external cellular membrane of
osteoblasts
Function is unknown???
Typically young, growing dogs
96% of total ALP in patients <1 yr
Only 25% of total ALP in patients >8 yr
Other causes of increased B-ALP
Osteosarcoma
Typically <4x normal
Prognostic
Fx healing, renal 2nd hyperparathyroidism,
nutritional osteopathies (rare)
Benign familial hyperphosphatasemia
Siberian huskies
Corticosteroid Alkaline Phosphatase
Remember in dogs only!
C-ALP 10-30% in normal dogs
Product of the I-ALP gene expression in the liver
Expression delayed in experimental dogs
% of total ALP increases with age
Can be measured at most labs but…
What does it mean???
Very high sensitivity for Cushing’s (95%)
Very poor specificity (18%)
Liver Alkaline Phosphatase
Located predominantly in the periportal zone
Bile canaliculi and sinusoidal membranes
L-ALP is predominate isoenzyme in dogs >1 yr
Two mechanisms for increase
Cholestasis
Drug induction
Phenobarbital
Exogenous steroids
Differentials for increased ALP
B-ALP
C-ALP
Intrahepatic cholestasis
Nodular hyperplasia, Neoplasia, Chronic hepatitis/cirrhosis, Vacuolar
hepatopathy, Infectious/inflammatory, Toxic, hepatocutaneous syndrome
Extrahepatic cholestasis
Pancreatitis, Biliary disease, Mucocele, Cholangitis/cholangiohepatits,
Neoplasia (biliary, duodenum, pancreas), Cholelithiasis
Secondary/reactive
Cushing’s, exogenous corticosteroids
Cholestasis
Young animals, bone neoplasia, nutritional osteopathy, hyperparathyroisim
Chronic disease-Neoplasia, infection/inflammation, pancreatitis
Gastrointestinal disease
Endocrine (hypothyroid, DM, hypertriglyceridemia in Min. Sch.)
Induction (drugs)
Breed-related
Siberian huskies, Scottish terriers
Common conditions causing only
increased ALP
Cushing’s disease
Drug induction
Idiopathic vacuolar hepatopathy
Hepatic neoplasia
Nodular hyperplasia
Breed-related
How high is too high???
Degree of increase does not correspond with
degree of illness
Dogs with ALP associated disease
Makes it more likely?
1,950 +/- 1,300 U/L
Dogs without disease
970 +/- 430 U/L
(Nestor et al.)
Does high ALP cause signs?
NO!!!
No patient has ever died from a
high ALP
There is little/no evidence that high
ALP makes you ill
The enzyme does not do the harm the
underlying disease does
The diagnostic dilemma begins
Review the record!!!
Signalment
Clinical history
Drug history
Physical examination findings
Questions to ask yourself…
What is the patient’s age and breed?
What medications is the patient on?
Topicals and inhaled
WHY was the blood work performed?
Is the elevation repeatable?
More questions to ask…
Any clinical signs of Cushing’s dz?
Other biochemical changes?
Before the blood work was performed?
Hepatic, biliary or pancreatic disease?
Does the patient have any evidence of
systemic illness?
Beyond a CBC, Chemistry and UA
Abdominal ultrasound
Endocrine testing
Urine cortisol:creatinine ratio
LDDS
ACTH stimulation test
Tennessee adrenal panel
Bile acids
Liver aspirate/biopsy
Valley Fever titer???
Thoracic radiographs???
How to avoid running every test…
There is no “best” order to perform
diagnostic tests for all patients
Diagnostic plans should be
individualized
Minimize invasiveness
Maximize owners financial resources
“Rainy” Bates 9 yr FS Aussie mix
Presented for PU/PD, very happy otherwise
PE – Dorsal alopecia, slightly pendulous abd.
Initial ALP was 2200 U/L, ALT 300
USG 1.012 with 2+ protein
“Rainy” Bates 9 yr FS Aussie mix
What is the patient’s age and breed?
What medications is the patient on?
None
Why was the blood work performed?
Middle aged FS Aussie X
PU/PD
Is the elevation repeatable?
No
“Rainy” Bates 9 yr FS Aussie mix
Any clinical signs of Cushing’s dz?
Other biochemical changes?
YES!
No
Does the patient have any evidence of
systemic illness?
No
“Rainy” Bates 9 yr FS Aussie mix
Abdominal ultrasound
ACTH stimulation
Bilateral enlarged adrenal glands
Homegenously enlarged liver
Consistent with Cushing’s Dz – go figure
Lysodren therapy
ALP 245 U/L
“Fionna” 8 yr FS Scottish Terrier
Presented for dental
Initial ALP 650 U/L, ALT WNL, USG 1.024
Dental was performed with no complications
Normal clinically
Post-procedural antibiotics for 10 days
ALP eight weeks later was 960 U/L
16 weeks later patient ALP was 830 U/L
Owners now say Fionna may increased thirst
“Fionna” 8 yr FS Scottish Terrier
What is the patient’s age and breed
What medications is the patient receiving
None (1 round of antibiotics)
Why was the blood work performed?
Middle age Scottish terrier
Pre-op Dental
Is the elevation repeatable?
Yes
“Fionna” 8 yr FS Scottish Terrier
Are there any clinical signs of Cushing’s
disease?
Are there other biochemical changes
suggestive of hepatic, biliary or pancreatic
disease?
???
No
Does the patient have any evidence of
systemic illness?
No
Next step?
UA
Abdominal ultrasound
WNL
ACTH stimulation
USG 1.020
No proteinuria
Pre – 7
Bile acids
WNL
Post - 18
Liver Biopsy
Vacuolar hepatopathy
More???
Tennessee Adrenal panel
17-hydroxyprogesterone was increased
Thank goodness!
Refer to trusty Tennessee Adrenal panel treatment
options worksheet
Apparently healthy Scottish Terriers
Nestor et al.
Had significantly higher mean serum ALP activity
then control dogs
2.4 times more likely to have a disease associated
with high ALP
Zimmerman et al.
More likely to have exaggerated adrenal panel
and histological changes
12/17 w/high ALP
10/17 dogs in control group
“Rusty” Hughes 4 yr MN Labrador
Previously dx with CNS Valley Fever
Phenobarbital, prednisone, fluconazole x 4 mo.
2 weeks after starting meds ALP 1050 U/L
11,500 U/L – 1 mo. (put on SAM-e)
29,000 U/L – 4 mo.
32,000 U/L – 5 mo. (0.5 mg/kg/d)
Evidence of iatrogenic Cushing’s disease
“Rusty” Hughes 4 yr MN Labrador
What is the patient’s age and breed
What medications is the patient receiving
Prednisone, Pb, Fluconazole
Why was the blood work performed?
Young Labrador
CNS Valley Fever
Evidence of iatrogenic Cushing’s
Is the elevation repeatable?
Yes
“Rusty” Hughes 4 yr MN Labrador
Are there any clinical signs of Cushing’s
disease?
Are there other biochemical changes
suggestive of hepatic, biliary or pancreatic
disease?
Yes
???
Does the patient have any evidence of
systemic illness?
Yes
“Rusty” Hughes 4 yr MN Labrador
Abdominal ultrasound
Enlarged and uniformly hyperechoic liver
Gallbladder WNL
Further plan?
Taper off of steroids and phenobarbital!
“Rusty” Hughes 4 yr MN Labrador
1 mo. off of steroids
Owner gave 2-3 dosage of steroids
1,335 U/L
ALP 2,200 U/L
Currently only on Fluconazole and
Zonisamide
ALP 750 U/L
“Zoe” Marsh 9 yr FS Lhasa Apso
History of IMHA
ALP 190 U/L – Prior to tx
Abdominal U/S – WNL
ALP 540 U/L – During therapy (2 mg/kg)
In complete remission and off of therapy for 9 mo.
Presented for recheck
Clinically normal
ALP 840 U/L
Rest of CBC/Chem/UA WNL
“Zoe” Marsh 9 yr FS Lhasa Apso
UCC - WNL
Repeat abdominal U/S
Placed on antibiotics and ursodiol
“Sludge” in the Gallbladder
Maintained on ursodiol
Started SAM-e
5 months later…
ALP 2780 U/L
Cholesterol is 420 mg/dL
Mild non-regenerative anemia (HCT 35%)
“Zoe” Marsh 9 yr FS Lhasa Apso
What’s the patient’s age and breed
What medications is the patient receiving
Hx of steroids - none recently
Ursodiol for previous 5 mo.
SAM-e for previous 2 mo.
Why was the blood work performed?
Middle aged Lhasa
Monitoring of ALP
Is the elevation repeatable?
Yes…and increasing
“Zoe” Marsh 9 yr FS Lhasa Apso
Are there any clinical signs of Cushing’s
disease?
Are there other biochemical changes
suggestive of hepatic, biliary or pancreatic
disease?
No
Gallbladder “sludge”
Does the patient have any evidence of
systemic illness?
Yes – Mild non-regenerative anemia
Plan???
ACTH
stim?
Bile Acids?
Liver Bx?
What I did…
Total T4 – WNL
Repeat abdominal ultrasound
Surgery???
Cholecystectomy + Bile culture + Liver biopsy
Bile culture
GB histopathology
Negative
Biliary mucocele
Liver histopathology
Mild-moderate vacuolar hepatopathy
Follow-up
Continued ursodiol
ALP 2 months after surgery
345 U/L
“Roxy” Milho 10 yr FS Rottie mix
Poor appetite and weight loss for last 23 months
ALP is 278 U/L
Rest of Blood work/UA is non-remarkable
Several drug trials including recent
prednisone
“Roxy” Milho 10 yr FS Rottie mix
What’s the patient’s age and breed
What medications is the patient receiving
Has been on steroids recently
Why was the blood work performed?
Old Rottie mix
Decreased appetite and weight loss
Is the elevation repeatable?
???
“Roxy” Milho 10 yr FS Rottie mix
Are there any clinical signs of Cushing’s
disease?
Are there other biochemical changes
suggestive of hepatic, biliary or pancreatic
disease?
No
No
Does the patient have any evidence of
systemic illness?
Yes
In conclusion…
Focus on the patients’ clinical signs as much
(if not more) then the degree of increase
Finding a cause requires a systematic
approach
Remember your pathophysiology
Thoroughly review the record
Ask yourself the “ALP” questions
Develop a tailored patient plan
QUESTIONS???