Thread by @ClementLeeMD

1/17
When should I send an ammonia? A thread 🧵 and list of indications

#MedTwitter #TipsForNewDocs

2/17
As I mentioned previously, ammonia is commonly sent for workup of AMS, and rarely is it helpful in that setting.

https://twitter.com/ClementLeeMD/status/1539011401037107207?s=20&t=rqDrd4qsekOvLxntIpOSZA

3/17
There are many reasons for this, one being ammonia needs to be sent from free-flowing samples and on ice. 🩸🧊

Also, it cannot be used to rule in or out hepatic encephalopathy, which is a clinical diagnosis.

4/17

However, in which population is an ammonia level helpful?

5/17
Trick question; answer is all of the above, but with targeted testing. ‼️

Let’s examine these situations in more detail. 🔍

6/17
The most well-known indication for ammonia testing is probably acute liver failure. In ALF, ammonia levels correlate with poor outcomes, including cerebral edema 🧠 (PMID 17685471).

This can help risk-stratify for transplant. 🧮

7/17
Now we get to some esoteric causes. 🦓

In oncology patients, specific cancers and chemotherapies can lead to an encephalopathy syndrome involving ammonia.

8/17
Myeloma encephalopathy involves some myeloma cells generating ammonia and may respond to therapy for myeloma. 🦀

Dialysis in this setting is less clear (PMID 12024007).

9/17
Many chemos can cause AMS w high ammonia; 5-FU is most famous. 😷🧪

5-FU induced encephalopathy occurs in 5% of pts receiving high doses. It may be 2/2 metabolism defects (DPD deficiency) or 5-FU inhibiting urea cycle --> acquired urea cycle d/o (PMID 26942162).

10/17
Now my favorite population: kids! 👶

If suspecting a urea cycle disorder (UCD), like in a baby w respiratory alkalosis and 🔼 LFTs, send ammonia. UCDs can also be 2/2 organic acidemias, where there are other findings (cardiomyopathy 💔, pancytopenia, kidney injury).

11/17
Another rare syndrome in kids is HI/HA (hyperinsulinism-hyperammonemia) syndrome. There's hypoglycemia (due to HI) and protein intolerance.

Interestingly, these kids don't get encephalopathy, though many have epilepsy.

I saw some cases at CHOP:

chop.edu/stories/hyperi…

12/17
Post-surgical patients -- 2 specific types -- may also have syndromes involving elevated ammonia.

First, transplant patients (specifically lung) 🫁 can be infected with Ureaplasma or M. hominis --> encephalopathy 2/2 generation of ammonia. Can be fatal. (PMID 32420020)

13/17
Second, post-gastric bypass patients can have encephalopathy w high ammonia.

This is postulated to be due to bacterial overgrowth🦠producing ammonia + zinc deficiency (which can cause a secondary UCD). (PMID 25954483)

14/17
Finally, some psychiatric indications.

A commonly cited indication is in teasing out seizure vs. PNES (aka pseudoseizure). Although not specific, ammonia, along with prolactin (minutes), lactate (hours), and CK (days later) can all be helpful. 🧠⚡️

15/17
And… add a psych drug toxicity to the list. In those taking valproic acid (VPA), toxicity often involves high ammonia. 💊

VPA is thought to inhibit one of the enzymes of the urea cycle. However, not all patients w high ammonia levels become confused. (PMID 6810855)

16/17
That rounds up my list! I don’t fault clinicians for sending ammonia for AMS, but I will push them to see what specifically they are looking for. 🤔

Like all tests, ammonia should be ordered with a pretest probability and dx in mind, not as a shot in the dark. 🎯

17/17
#MedTwitter, can you think of other indications?

@AaronLBerkowitz @rabihmgeha @TimRoweSays @DxRxEdu @DrHarryThomas @cameron_baston