My veterinarian just told me that my dog’s alkaline phosphatase levels are high. What is alkaline phosphatase?
Alkaline phosphatase is an enzyme that is found in your dog’s bloodstream. We commonly refer to this enzyme as ALP or ALK PHOS. There are three versions of the enzyme: 1) Bone‐ALP, 2) Liver‐ALP, and 3) Corticosteroid induced‐ALP.
How common is high ALP?
A high ALP value is a very common lab finding. 39% of all dogs have a high ALP and 51% of dogs over 8 years have a high ALP. Because there are so many causes of a high ALP, many of which are benign (harmless) processes, determining the cause of an individual patient’s high ALP can be a diagnostic dilemma!
My puppy is only 5 months old and has a high ALP in pre-surgical blood screening. What could be causing my puppy’s high level of ALK PHOS?
When we see a high ALP in a growing patient, we usually assume that the cause of the high ALP is growth, which stimulates Bone‐ALP. Bone‐ALP actually accounts for ~96% of the total ALP in patients less than 1 year of age. As patients age, this changes, and only 25% of total ALP in patients over 8 years of age is from Bone‐ALP. This type of elevation in ALP is expected and not worrisome at all.
My senior dog has a persistently high ALP and my vet says it might be Cushing’s disease.
What is Cushing’s disease and why would it cause a high ALP? How do we figure out if my pet has Cushing’s disease?
In Cushing’s disease the adrenal glands (located near the kidneys) are in over‐drive in their production of steroid hormones. There are different causes of Cushing’s disease, but all causes produce similar symptoms which may include increased thirst, hunger, urinary accidents (secondary to the increase in water intake), a pot‐ belly appearance, thinning of hair coat, patchy loss of the hair coat over the back of the body, and sometimes secondary skin infections and ear infections (bacterial infections or yeast infections). Pets with Cushing’s disease may have urinary tract infections, as well, because the excess circulating steroids act to suppress the immune system.
Cushing’s disease causes a high ALP because of the excess steroid in the body. We call this corticosteroid‐induced ALP.
When we see a high ALP in a senior dog without any increases in ALT, another liver value, we always place Cushing’s disease on our list of potential causes. If the patient, however, has no symptoms of Cushing’s disease, we usually don’t pursue
any immediate testing and will recheck the ALP about a month later. If the patient has symptoms of the disease, then we have several options for ruling in Cushing’s disease, which may include abdominal ultrasound along with further blood tests or a specific urine test that can rule out Cushing’s disease (if this test is normal we know that your pet does NOT have Cushing’s disease).
My senior dog has a higher than normal ALP without any increase in the ALT liver value, and no symptoms of Cushing’s disease. He has no signs of illness. We rechecked the ALP value 1 month and 3 months after we saw the initial elevation and it hasn’t increased at all. How concerned do we need to be about this high ALP?
Where to go with this particular case may depend on how high the ALP is and how much testing a client wants to pursue. There can be worrisome issues such as liver cancer that start out with a higher ALP. Often, though, we may see a higher ALP in senior patients that may wax and wane slightly with each subsequent year, staying roughly the same. Many of these patients have a liver condition called “nodular hyperplasia.” This condition does not cause illness for the patient. A definitive diagnosis of this harmless condition needs to be made via biopsy (and then histopathology), but often we suspect it if the ALP does not do much over months or years. It is a very common, age‐related, incidental liver finding in dogs. The reported incidence is from 70‐100% in dogs older than 14 years of age. For the particular patient above, I would recommend rechecking the ALP again in 6 months and 1 year. If the ALP stays roughly the same and the patient has no signs of illness or symptoms of Cushing’s disease, rechecking the ALP every 6 months would then be reasonable.
My dog has a higher than normal ALP value and takes phenobarbital to control seizures. Is this something I need to worry about?
Some drugs, such as phenobarbital and steroids, cause an increase in ALP values via induction of liver‐ALP. Although an increase in liver values does not always mean there is an issue brewing, toxic insult to the liver is a concern for these patients, and either further testing should be conducted or the patient should be weaned off phenobarbital as they transition to another anti‐seizure medication. The ALP would then be rechecked 2‐4 weeks later—at this time we would expect it to normalize if the increase was due to the phenobarbital use. In the case of weaning from steroids, it may take several months for the ALP to normalize.
If my dog has an increased ALP and we want to get to the bottom of the cause, what tests are available?
Blood tests are usually the first thing we look at. If the initial chemistry profile was a limited profile, we’ll then order a comprehensive chemistry panel that lets us examine other liver values (ALT, GGT, AST) or tests of liver function (bilirubin, bile
acids, albumin). Along with a comprehensive profile, a complete blood count and urinalysis are important. Abdominal x‐rays may allow us to assess the shape and size of the liver, but abdominal ultrasound is much more sensitive. Chest x‐rays may also be recommended. During an ultrasound, a liver aspirate or biopsy may be obtained. Lastly, if an endocrine issue such as Cushing’s disease is high on the list, tests may include a urine cortisol:creatinine ratio, a low dose dexamethasone suppression (LDDS) test, an adrenocorticotropic hormone (ACTH) stimulation test, or an adrenal panel.
Beyond what was discussed in the questions above, what are other things that may cause an increase in the liver value ALP?
The list is very long (too long for the scope of this article!), but may include: hyperparathyroidism or hypothyroidism (other endocrine disorders), breed‐related predispositions, bone cancer, chronic liver inflammation (hepatitis or cirrhosis), liver infection/inflammation, toxin exposure, pancreatitis (inflammation of the pancreas), bile duct disease, gall bladder disease (including gall bladder stones, mucoceles, or obstruction), cancer of the bile duct, duodenum, or pancreas, secondary/reactive diseases such as cancer, infections, inflammation not related to the GI tract, or gastrointestinal disease (can be as simple and temporary as gastrointestinal upset after getting into the garbage).
As one can see from this non‐comprehensive list, there are many directions one could go in trying to diagnose the cause of increased ALP. Because of the variety of potential causes, every case of an increased ALP is handled differently and there is no standard approach for handling each case and no “best” order to perform diagnostic tests for all patients.