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Gilbert’s Disease

            Previously with Medgeeks, we’ve covered sessions on “abnormal labs”. As a new graduate, or as a seasoned provider sitting in front of a new patient, it can be difficult to sort through lab work to determine whether an abnormality is truly concerning, or the patient’s baseline.

            In primary care, some of my more diligent patients are very inquisitive when it comes to their lab work. I will get online messages asking “Why the anion gap is 13 when it should be 12”, or appointment requests to discuss why a chloride or “globulin” level was abnormal. As clinicians, we have to be sure that we are able to sort through the abnormal and normal to provide the best care for our patients, sometimes this means ignoring lab work that is not of clinical significance.

Critical Lab Results & Gilbert’s Disease

            Of special note, in the case of Gilbert’s Disease, we must first notice the abnormal lab value, then assure ourselves through a workup that there is no concerning condition present. Today, we will be reviewing Gilbert’s Disease/Syndrome.

What is Gilbert’s Disease?

            Gilbert’s disease is a chronic or intermittent disorder where patients experience chronically elevated unconjugated (indirect) hyperbilirubinemia, with normal intrinsic liver function (Marlow, 2016).

            As we will recall from our anatomy and physiology days, there are four main pathways for bilirubin metabolism:

  1. Uptake in the circulation
  2. Cellular storage
  3. Conjugation
  4. Excretion.
  5. Most of the body’s bilirubin is unconjugated (indirect). An error or pathology in any one of the above steps can result in an increased uptake of bilirubin; as seen in cirrhosis and chronic liver disease. The remaining process for bilirubin conjugation, metabolism, and excretion is complex and goes beyond the scope of today’s focus (Roy-Chowdhury 2019).

Prevalence

            Gilbert syndrome is a benign condition that results in hyperbilirubinemia. In the United States, this is one of the most common causes of elevated bilirubin, impacting up to 7% of the population. As an interesting side note, which does relate clinically, up to a third of those patients impacted, have no idea (Marlow, 2016). The lack of knowledge can sometimes cause clinical concern, because when we order routine lab work to find that the bilirubin is elevated, patients start to get very worried that something is wrong, this further escalates when we begin asking them about a family history of liver problems, or other related questions.

Pathophysiology        

            The pathophysiology of Gilbert’s syndrome is believed to be a result of a decreased bilirubin clearance, usually about 30 to 40% of normal. The conjugation of bilirubin is decreased, resulting in excess levels in the serum. The remaining pathology of Gilbert’s syndrome is not well understood, and is thought to be multifactorial (Marlow, 2016).

History and Physical Exam    

            The vast majority of patients with Gilbert’s syndrome are without any identifiable symptoms. The history may show a previous family history of “liver disease”, which turns out to be benign. In many cases, patients may simply refer to the disorder as “liver disease” because they do not know the exact name. In some cases, patients will give a history of cyclical episodes of jaundice of unknown origin, around times of stress, acute illness, lack of sleep, physical exertion, dehydration, menses, or surgery. There are classically no other symptoms of acute or chronic liver disease present.

            As discussed above, the vast majority of patients are entirely asymptomatic and thus the physical exam is usually not particularly helpful, as it is traditionally normal. Occasionally, if the patient comes in with an acute concern of having jaundice during an episode, usually brought on by of one of the above-mentioned triggers, the clinician may be able to identify jaundice on examination. Unfortunately, there are traditionally no other physical exam findings that point towards the diagnosis. The clinician should be cautious to screen for other disorders such as cirrhosis, acute liver injury, other abdominal pathology and perform a thorough history and physical examination as part of the workup for any patient complaining of jaundice.

The Hallmark

As discussed above, the hallmark of Gilbert’s disease is a sole increase/elevation in indirect bilirubin. According to Marlow (2016), the bilirubin level is usually less than 6 and commonly between 1 and 3. Direct bilirubin is most often normal.

Additional Laboratory Tests & Diagnostics

            Other lab work including; AST, ALT and Alkaline phosphatase are normal, along with coagulation factors PT/INR, GGT and other intrinsic liver function tests. In the case of the young patient, usually there is no specific work up as long as the patient has no other symptoms. It is important to note family history as sometimes this may be your only clue. In the patient with significant alcohol use, fatty liver disease, or other comorbidities, other ancillary testing to rule out other causes may include liver ultrasound, but this is usually not needed.

Isolated Elevation in Bilirubin & Screening

            Obviously there are cases where other diagnoses could be at play. Marlow (2016) recommends that in the case of an isolated elevation in bilirubin, patients be re-checked 2 to 3 times over a period of 12 to 18 months. As long as there are no other symptoms, or elevations in other liver enzymes, the diagnosis can be made.

Treatment

            The treatment of Gilbert’s disease is reassurance. It is a benign, self-limiting condition that does not require any type of intervention. In many cases, the diagnosis can be worrisome for patients, as it sometimes requires monitoring and repeat lab work. Once other liver pathology has been ruled out, the patient can be reassured that nothing else needs to be done and their symptoms will remit.

Patient Counseling

            In my own experience, I find that it is helpful to make patients aware of what the diagnosis is and if they are changing PCPs or moving out of the area, I inform them that they should be sure to tell their new healthcare provider of the diagnosis to avoid repeating a work up. Though, this should always be done whenever a patient changes providers.

References

Marlow, R.A. (2016). Gilbert Disease. 5 Minute Clinical Consult Wolters Kluwer.

Roy-Chowdhury, J (2019). Gilbert Syndrome and unconjugated hyperbilirubinemia due to bilirubin overproduction. UpToDate. Date of Access 25 October 2019.