My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I go through a real-life case of an asymptomatic patient with an isolated raised alkaline phosphatase level. I will describe a recommended approach to investigate and manage them according to guidelines. 

I am not giving medical advice; this video is intended for health care professionals; it is only my interpretation of the guidelines and you must use your clinical judgement.  

There is a YouTube version of this and other videos that you can access here: 

·      The NICE GP YouTube Channel: NICE GP - YouTube 

You can download a summary of my summary / interpretation of the guidance here:  

·      My Summary: https://1drv.ms/b/s!AiVFJ_Uoigq0mC4pm_bYELFa9wEx?e=07p2dJ

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Transcript

Interpreting Isolated Raised Alkaline Phosphatase in Asymptomatic Patients

Hello and welcome. I’m Fernando, a GP in the UK. Today, we're going to explore what to do when we encounter an isolated raised serum Alkaline Phosphatase level in an asymptomatic patient. Please like and subscribe to support the channel.

Right, so let's dive right in!

Introduction

Before we start, let’s remember that Alkaline Phosphatase is present in various tissues, including the liver, bone, kidney, intestine, and placenta. Reference ranges can vary with age and gender, so mild increases may not indicate disease.

Examples of Physiological Causes are:

·      Growth spurts in adolescents

·      Pregnancy in women

·      Age-related increases and

·      Medications like some antibiotics, antiepileptics, antihistamines, oestrogens, and steroids

Some potential causes of isolated raised serum Alkaline Phosphatase include:

·      Congestive cardiac failure

·      Bone diseases

·      Hyperthyroidism

·      End-stage renal disease

Clinical case

So, let’s have a look at our patient. She is a 49-year-old lady who had some blood tests because she was feeling a little tired. Her results came back normal with the exception of an alkaline phosphatase level of 186 (NR 30-130). Physical examination was normal and that there were no signs or symptoms of disease. In addition, she does not drink alcohol at all.

What should be our next steps?

The baseline investigations for someone with an isolated Alkaline Phosphatase are the following tests:

·      Liver function tests adding GGT

·      Calcium and phosphorus adding vit D and PTH

·      Renal and thyroid function tests and

·      A full blood count

We know that the most likely sources of Alkaline Phosphatase are either the bone or the liver. And, in order to differentiate between them, this is why we measure GGT (which is typically elevated in liver issues) and vitamin D levels and PTH levels, which may point towards bone causes.

So, for this patient we will need to repeat the Alkaline Phosphatase levels and checking gamma-GT, vitamin D and parathyroid hormone to try to determine the cause, as well as making sure that the other tests, that is, renal, and thyroid function tests, calcium, phosphorus and a full blood count have also been checked

We will talk more about our patient a little later but now let’s say that, in general terms, if all these tests come back normal, further investigations can be deferred for three months, during which Alkaline Phosphatase levels should be rechecked. Rechecking it earlier than three months is generally unnecessary unless you have specific concerns.

If Alkaline Phosphatase is raised with elevated GGT levels, it's likely of hepatic origin. Further steps that we will need to consider include:

·      Abdominal ultrasound scan (to check for cholestasis and hepatic space-occupying lesions)

·      Antimitochondrial antibodies test (to explore the possibility of primary biliary cirrhosis)

However, if these liver investigations are normal, and the Alkaline Phosphatase level is less than 1.5 times the upper reference limit, observation and monitoring every 3 to 6 months is recommended.

However, if the Alkaline Phosphatase level is more than 1.5 times the upper reference limit and a hepatic origin is suspected, referral for further liver investigations is recommended.

Now, if GGT levels are normal, the raised Alkaline Phosphatase is most likely from a non-hepatic source, often bone-related. This can be due to vitamin D deficiency, Paget's disease of bone, or growth spurts in adolescents.

And how do we manage this? Obviously, if the vitamin D levels are low, we will treat the deficiency accordingly. And if there is any abnormality in the PTH levels, we will also manage it and investigate it further.

If Vitamin D and PTH are normal and if the Alkaline Phosphatase level is less than 1.5 times the upper reference limit and we have no clinical concerns, then observation and monitoring every 3-6 months is usually enough.

However, for those with non-hepatic Alkaline Phosphatase levels more than 1.5 times the normal level, bone scintigraphy may be considered to detect conditions like asymptomatic Paget's disease.

In cases of diagnostic uncertainty and significant increases in serum Alkaline Phosphatase, checking Alkaline Phosphatase isoenzymes will be considered. This will be more precise in determining the origin of the raised levels.

So, there we have it, a guide on what to do when you encounter an isolated raised serum Alkaline Phosphatase level in an asymptomatic patient.

But, what happened to our patient?

Repeat testing showed normal results including GGT, Vitamin D and PTH but the Alkaline Phosphatase went from 186 to 204. Her history and examination remained unremarkable but she started to complain about some abdominal discomfort.

Because of the rise in the Alkaline Phosphatase level and her symptoms, as a precaution, an USS of the abdomen was arranged as well as another check of her Alkaline Phosphatase 6 weeks later.

The results showed that the Alkaline Phosphatase was still high but it had decreased slightly to 191 and her USS showed steatosis of the liver.

So, we conclude that she has non-alcoholic fatty liver disease or NAFLD. Although her liver function tests and GGT results were normal, it is likely that the raised Alkaline Phosphatase level is due to this.

By the way, if you are unsure about how to diagnose and manage NAFLD, please check the corresponding episode on this channel.

By the way, if you are unsure about how to diagnose and manage NAFLD, just click here or in the link that I have put in the episode description which will take you to the corresponding episode on this channel.

And because the Alkaline phosphatase level is less than 1.5 times the upper limit of normal, we will monitor it every 3-6 months.

Remember, that this is not medical advice, it is only my summary of the guidelines consulted and you must use your clinical judgement.

Thanks for watching, and goodbye!

Thank you for listening and goodbye!