Published December 18 2017
Many people with hyperthyroidism and Graves’ Disease have elevated liver markers. This includes the liver enzymes ALT and AST, along with alkaline phosphatase. The reason why elevated liver markers are a concern is because this indicates that liver damage is taking place. In this article I will talk about why these markers are commonly elevated in those with hyperthyroid conditions. I’ll also discuss other health conditions that can affect these markers, and I’ll also talk about the different options you have.
Although I assume that most people reading this have already had a test which revealed elevated liver markers, there probably are a few people reading this who haven’t had such testing done. And so before talking about the different markers, I’ll start off by saying that anyone with a hyperthyroid condition (i.e. Graves’ Disease, toxic multinodular goiter [1]) should obtain a comprehensive metabolic panel (CMP). This is especially important for those taking antithyroid medication, but even if you’re not taking Methimazole or PTU, a CMP is a test offered by just about all labs, and it’s also a test that most medical doctors won’t have a problem ordering.
In fact, most medical doctors, including endocrinologists, will order a CMP for their hyperthyroid patients who are on antithyroid medication. But of course there are always exceptions, as over the years I have come across a few patients with hyperthyroidism who didn’t get this panel done, even though they were taking antithyroid medication. Keep in mind that some doctors won’t order a CMP, but instead will offer a hepatic function panel, which is fine. You just want to make sure to get a blood test that measures the three markers I’m about to discuss.
Three Liver Markers That Are Commonly Elevated In Hyperthyroidism and Graves’ Disease
The following are the three liver markers that should be measured in everyone with hyperthyroidism:
1. Alanine aminotransferase (ALT). Also known as serum glutamate-pyruvate transaminase (SGPT), this is a liver enzyme whose elevation indicates liver damage. ALT is more commonly elevated than AST. ALT is mainly found in hepatocytes (liver cells). When damage to the liver occurs, ALT is released from injured liver cells, and this causes an elevation of serum ALT (1) [2]. ALT is also present in muscles, adipose tissue, the intestines, colon, prostate, and brain (1) [2]. It’s also worth mentioning that extreme exertion (i.e. running a marathon) can cause a temporary elevation of the liver enzymes.
2. Aspartate aminotransferase (AST). Also known as serum glutamic oxaloacetic transaminase (SGOT), this is another liver enzyme that can be indicative of damage to the liver when it’s elevated. In addition to being found in the liver, AST is also located in the heart, kidneys, brain, and skeletal muscles. Whereas ALT can increase up to 50 times greater than normal when liver damage is present, AST levels will typically rise 10 to 20 times greater than normal (2) [3]. One reason for this is because ALT is more specific to the liver, and so if ALT is elevated this is usually a pretty good indication of liver damage. On the other hand, if AST is elevated and ALT is normal then chances are that damage is happening to a different area of the body, such as the skeletal muscles.
3. Alkaline Phosphatase. This is an enzyme that is found in the bloodstream, and it plays a key role in metabolism within the liver. However, when it is elevated not only can it indicate problems with the liver, but it also can indicate a problem with the bones and/or gallbladder. Elevated alkaline phosphatase can not only be an indication of hyperthyroidism, but other health problems as well such as hepatitis, cirrhosis, cholecystitis, a blocked bile duct, osteomalacia, bone cancer, or hyperparathyroidism [4].
Why Do These Liver Markers Become Elevated?
Hyperthyroidism. It is very common to see elevated alkaline phosphatase levels in someone with hyperthyroidism. This is true whether the person’s hyperthyroidism is due to Graves’ Disease, or another condition, such as toxic multinodular goiter. On the other hand, while sometimes the liver enzymes (AST and ALT) will be elevated due to hyperthyroidism alone, this isn’t as common.
Antithyroid medication [5]. Elevated liver enzymes are common in those people who are taking antithyroid medication. This is especially true with Propylthiouracyl (PTU), as this puts more stress on the liver than Methimazole or Carbimazole. In fact, research shows that PTU-related liver toxicity is likely to occur in about 1% of treated patients, and liver failure may occur in about one third of those who experience liver toxicity (3) [6]. However, I should mention that I have seen elevated liver enzymes in a lot of people who were taking other types of antithyroid medication, including Methimazole. This is why the liver enzymes need to be tested regardless of what type of antithyroid medication someone is taking.
Alkaline phosphatase doesn’t typically increase when someone takes antithyroid medication. In fact, when someone takes antithyroid medication the alkaline phosphatase will frequently decrease due to the thyroid hormones decreasing. If the alkaline phosphatase doesn’t decrease soon after normalization of the thyroid hormones occur then this usually indicates another problem. One possibility is a condition called thyroid acropachy [7], which is characterized by soft tissue swelling and periosteal bone changes.
Other Reasons For Elevated Liver Enzymes:
Viral hepatitis. If someone has very high levels of liver enzymes this might not be caused by antithyroid medication, but an acute case of hepatitis should be suspected (4) [8]. With viral hepatitis the liver enzymes can stay elevated for a few months. On the other hand, chronic hepatitis will present with elevated liver enzymes as well, although not quite as high as acute hepatitis.
Frequent alcohol consumption. Since alcohol puts stress on the liver it shouldn’t be surprising that drinking a lot of alcohol on a frequent basis can cause the liver enzymes to be elevated.
Family history of liver disease. Although genetics can’t be overlooked, this usually isn’t the cause of elevated liver enzymes or a high alkaline phosphatase. An exception is a family history of liver cancer or hepatocellular carcinoma (5) [9].
Other medications. In addition to antithyroid drugs, other medications that can sometimes cause elevated liver enzymes include aspirin, acetaminophen, ibuprofen, antibiotics, anti-fungal medication, anti-seizure medication, statins, and certain cardiovascular drugs, such as amiodarone (6) [10].
Non-alcoholic fatty liver disease [11] (NAFLD). Although not everyone with NAFLD has elevated liver enzymes, many people with this condition do have these markers elevated, with ALT usually being higher than AST (7) [12]. Other common findings include high triglycerides, low HDL levels, and sometimes the person will also present with high or high normal hemoglobin A1C levels (7) [12]. Obesity is the primary risk factor for the development of NAFLD, and there is also a strong relationship between NAFLD and type 2 diabetes (8) [13].
Other causes. Some other factors which can lead to elevated liver enzymes include hemochromatosis, autoimmune hepatitis, Celiac disease [14], and muscle injury.
When Should You Be Concerned About Elevated Liver Enzymes?
Although I become concerned when a patient’s liver enzymes are on the high side or elevated, regardless of what the specific value is, I wouldn’t panic if they are slightly above the lab reference range. On the other hand, if the liver enzymes are approaching or are over triple digits then this is a clear cause for concern. For example, the reference range for AST according to Labcorp is between 0-40 IU/L, and for ALT it’s between 0-32 IU/L. If someone’s levels are close to 100 IU/L, or greater than this value, then this without question is a cause for concern. This doesn’t mean that there shouldn’t be any concern if the number is below this value, as I would definitely monitor the liver enzymes while following the advice given below.
If the elevation of liver enzymes is due to antithyroid medication putting stress on the liver then the endocrinologist probably will tell you to stop taking it, or perhaps he or she will lower the dosage. Sometimes someone will have elevated liver enzymes when taking one type of antithyroid medication, but not another, and so at times the medical doctor will switch the patient to a different type. For example, while PTU usually isn’t the first option unless if a woman is in the first trimester of pregnancy, if someone happens to be taking PTU and has elevated liver enzymes, there is a chance that their liver enzymes won’t remain elevated if they switch to Methimazole. Unfortunately many endocrinologists will recommend radioactive iodine or thyroid surgery if the liver enzymes elevate in response to taking antithyroid medication, and they won’t consider other options.
When Should You Be Concerned About An Elevated Alkaline Phosphatase?
In this article I’ve been focusing more on the liver enzymes AST and ALT because these are usually a greater concern in those people with hyperthyroid conditions. As I already mentioned, the alkaline phosphatase is frequently elevated due to the high thyroid hormone levels, and as the thyroid hormone levels decrease this marker should also decrease.
The average reference range for alkaline phosphatase is 20–140 IU/L (Labcorp uses a range of 39-117 IU/L), and it’s common to see hyperthyroid patients with levels exceeding 200 IU/L. I’m not suggesting that an elevated alkaline phosphatase should be taken lightly, but the reason why elevated liver enzymes are a greater concern is because most of the time this is caused by taking antithyroid medication, and it’s suggesting that the medication is causing damage to the liver. And if the person is unable to take antithyroid medication then most endocrinologists will start pressuring the patient to receive radioactive iodine or thyroid surgery. But of course we want all three of these markers (AST, ALT, alkaline phosphatase) to eventually normalize.
What Options Do You Have?
If you have elevated liver markers and want to do everything you can to try to avoid radioactive iodine or thyroid surgery here are a few different options:
Option #1: Replace antithyroid medication with bugleweed or low dose naltrexone. If antithyroid medication is responsible for the elevated AST and/or ALT levels then stopping or decreasing the dosage of antithyroid medication might be necessary. Bugleweed is an option to consider, as this herb has antithyroid activity and it usually doesn’t result in an elevation of liver enzymes. While bugleweed usually does a great job of lowering thyroid hormone levels, it doesn’t work for anyone.
When this is the case then another option to consider is low dose naltrexone (LDN). This is a prescription medication, which might turn off some people, although it is much safer than antithyroid medication, as long term studies show that LDN doesn’t cause damage to the liver (9) [15]. LDN modulates the immune system, and while it isn’t always effective, it’s something worth trying if you are unable to take antithyroid medication and bugleweed doesn’t help. For more information please read an article I wrote entitled “Low Dose Naltrexone and Thyroid Autoimmunity [16]”.
Option #2: Lower the thyroid hormone levels. Lowering the thyroid hormone levels usually helps to decrease the alkaline phosphatase levels. As for the AST and ALT, if these markers are elevated due to the high thyroid hormone levels and not due to antithyroid medication or other factors I discussed earlier, then lowering the thyroid hormone levels will help. Of course lowering the thyroid hormone levels should be one of the main goals of anyone with hyperthyroidism, regardless if it is causing elevated liver enzymes.
Option #3: Support the liver. Milk thistle [17] is an herb that has hepatoprotective (liver protecting) properties and so this is something to consider taking if you have elevated liver enzymes. One study involving 72 patients with NAFLD showed that taking milk thistle resulted in a reduction of both AST and ALT (10) [18]. If a patient of mine is taking antithyroid medication I commonly recommend for them to take milk thistle, regardless of whether or not they have elevated liver enzymes.
It also can be beneficial to do other things to increase glutathione [19], which includes eating foods such as garlic, onions, and cruciferous vegetables. In fact, I came across two studies (one involving mice, the other a human study) which showed that broccoli can help to lower liver enzymes (11) [20] (12) [21]. Taking N-acetylcysteine (NAC) can also help to increase glutathione levels and lower liver enzymes, as a study involving 30 patients with NAFLD showed that NAC can significantly decreased ALT livers (13) [22]. Another option is to take an acetylated or liposomal form of glutathione. There is also evidence that alpha lipoic acid can help to decrease liver enzymes (14) [23]. Turmeric has some wonderful benefits, and there are a few studies which show that this can decrease liver enzymes (15) [24] (16) [25].
Just to make it easier to read I’ll include a list in bullet-point format of some of the things that can help to lower liver enzymes:
- Broccoli
- Milk thistle
- N-acetylcytsteine (NAC)
- Acetylated glutathione
- Liposomal glutathione
- Alpha lipoic acid
- Turmeric
In summary, it’s common for people with hyperthyroid conditions to have elevated liver markers. High thyroid hormone levels are usually responsible for the elevated alkaline phosphatase levels, although they can also be a factor in elevated AST and ALT levels. However, a more common reason for elevated liver enzymes is taking antithyroid medication. If this is the case then switching to a different type of antithyroid medication might help, although other alternatives include bugleweed and low dose naltrexone. If someone needs to take antithyroid medication it is a good idea to have them do things to support the liver, such as milk thistle, or increasing glutathione levels through food or supplementation.