Medications including aspirin, morphine, antiretrovirals, and estrogen-containing medication, can affect serum levels of amylase. Macroamylasemia, as referred above, is another well-recognized cause of elevated serum amylase. In this condition, the enzyme forms a complex with proteins such as immunoglobulins and polysaccharides[21]. Due to the large size of the macromolecular complex, renal clearance is reduced, causing persistently elevated amylase levels[22][7]. Macroamylasemia can occur in healthy individuals or in diseases including autoimmune disease, diabetes, and cancer such as thyroid cancer[23][24].

Urinary amylase is typically normal macroamylasemia and can help exclude the condition.  This condition occurs in 1 percent of healthy individuals and in 2.5 percent of individuals with hyperamylasemia. Macroamylasemia should be considered in an asymptomatic patient with elevated serum amylase. There is no required treatment for the condition[21]. Past studies have shown that macroamylasemia was primarily reported in patients with impaired humoral immunity, such as those with celiac disease, HIV infection, ulcerative colitis, rheumatoid arthritis, and multiple myeloma[25].

Currently, there is no internationally established reference range for amylase levels. The reference range can be as wide as 20-300 U/L. However, elevated amylase levels of more than three times the upper limit of normal strongly supports the diagnosis of acute pancreatitis. Less than this is often associated with other conditions[26]. Abnormally low levels of amylase is not common but can be observed in cystic fibrosis, chronic pancreatitis, diabetes mellitus, obesity, and smoking[8][27]. Clinicians should be aware of such causes to help to interpret low amylase activity in patients[8].

Amylase is primarily used in diagnosing pancreatic diseases. Amylase is a commonly measured enzyme due to the availability of inexpensive, easily automated methods[18]. Although amylase is a sensitive indicator of acute pancreatitis, it is not specific as it can be elevated in several conditions unrelated to the pancreas. Pancreatitis can be defined by two out of the three following criteria: abdominal pain, serum amylase and/or lipase levels more than three times the upper limit of normal, and abdominal imaging supporting characteristic findings of pancreatitis[28]. Therefore, its clinical significance has been questioned. In cases of elevated levels of amylase with little support for pancreatitis, alternative causes of hyperamylasaemia should be considered[20]. Amylase is not useful in predicting the severity of an acute pancreatic episode or monitoring the condition[29]. 

Amylase inhibitors such as acarbose have been used in the treatment of type 2 diabetes and have shown to reduce Hemoglobin A1C and peak postprandial glucose[30]. Acarbose has also been shown to improve remission of dumping syndrome in bariatric patients[31]. The drug also has also shown to improve the risk of cardiovascular disease by slowing down the thickening of carotid arteries[32]. Elevated amylase can be seen in a wide variety of conditions. It is important for clinicians to have a clear, stepwise approach when hyperamylasemia is found. This will help avoid unnecessary hospitalization and delayed or inappropriate treatment[22][7].

It is crucial that health care workers communicate effectively when laboratory results point towards a non-pancreatic cause. It is also important to be knowledgeable of the different conditions that may affect amylase levels[18]. Lipase is typically preferred instead of amylase due to higher specificity. Lipase typically stays elevated for up to two weeks, while amylase concentrations remain elevated for up to five days. Therefore, amylase is not as clinically useful as lipase if there is a delay between symptom onset and the time the patient seeks medical attention[26][29]. The 2013 American College of Gastroenterology mentions co-ordering lipase and amylase is neither cost-effective nor treatment advantageous. It also states that ordering amylase alone is unreliable and does not increase diagnostic efficiency compared to lipase[33]. If there is access to lipase testing, adding amylase simply increases the cost to the patient and has little value in supporting the diagnosis of pancreatitis[34][26].