Introduction: Who Should Undergo Diagnostics
Amyloidosis is frequently overlooked because its symptoms can look like those of many other, more common health problems. This can make the journey to a correct diagnosis long and frustrating for many people. Studies show that almost one-third of people with amyloidosis will see more than five different doctors before receiving the right diagnosis. Even more concerning, around 70% of patients will not be diagnosed for over a year after their symptoms first appear, and up to 20% may wait two years or longer before doctors identify the true cause of their health issues.[1][2][3]
If you are experiencing symptoms that don’t seem to go away or get better with usual treatments, it may be time to seek further testing. Common warning signs include severe tiredness that doesn’t improve with rest, unexplained weight loss without trying, shortness of breath that limits your daily activities, or swelling in your ankles and legs that persists. Some people notice numbness, tingling, or pain in their hands or feet, while others may develop skin changes such as easy bruising or unusual purple patches around the eyes. An enlarged tongue or digestive problems like diarrhea or constipation can also be indicators.[1][2]
Early diagnosis is particularly important because amyloid proteins can build up in vital organs like the heart, kidneys, liver, and nerves. The longer the disease goes undiagnosed, the more damage these protein deposits can cause. Research suggests that seeking medical help as early as possible can lead to an earlier and correct diagnosis, which in turn allows treatment to begin sooner and may prevent serious organ damage.[3]
People with certain existing health conditions may also be at higher risk and should consider diagnostic testing if they develop new or worsening symptoms. For example, individuals with long-term inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease like Crohn’s disease or ulcerative colitis, or chronic infections are more likely to develop a type called AA amyloidosis. Those with a family history of amyloidosis, especially if relatives have been diagnosed with hereditary ATTR amyloidosis, should discuss genetic testing with their doctor. Additionally, older adults, particularly men, may develop wild-type ATTR amyloidosis as they age.[2][5]
Diagnostic Methods for Identifying Amyloidosis
Diagnosing amyloidosis involves a combination of tests that help doctors identify whether abnormal proteins are present in your body, determine which type of protein is causing the problem, and assess which organs have been affected. Because symptoms can vary widely depending on where the amyloid deposits have formed, doctors use several approaches to piece together the full picture.[7][18]
Laboratory Tests
The diagnostic process usually begins with blood and urine tests. These laboratory tests look for abnormal proteins that can indicate amyloidosis. Doctors will analyze your blood and urine for specific markers that suggest the presence of amyloid-forming proteins. For example, they may check for abnormal light chain proteins in the blood, which are involved in AL amyloidosis. A test called serum free light chain (FLC) ratio analysis is commonly used to measure these proteins.[7][9]
In addition to protein tests, your doctor may order serum and urine protein electrophoresis to look for abnormal protein patterns. Another important test is the 24-hour urine collection, which measures the amount of protein being lost through the urine. This can help identify kidney involvement. Doctors may also check thyroid and kidney function through blood tests to see how well these organs are working.[7][9]
A complete blood count and chemistry panel provide additional information about your overall health and can reveal abnormalities that might point toward amyloidosis or help rule out other conditions.[9]
Tissue Biopsy
To confirm the diagnosis of amyloidosis, doctors need to see the amyloid protein deposits directly. This is done through a biopsy, which involves taking a small sample of tissue and examining it under a microscope. The tissue sample can reveal whether amyloid deposits are present and what type of protein is involved.[7][18]
There are several ways to obtain a tissue sample. One common method is a fat pad biopsy, where a small amount of fat is removed from under the skin on your belly. This is a relatively simple and minimally invasive procedure. Another option is a bone marrow biopsy, which takes a sample from the bone marrow, usually from the hip bone. If doctors suspect that a specific organ is affected, they may perform a biopsy of that organ. For instance, if your kidneys or liver show signs of damage, a biopsy of those organs can provide more detailed information about the extent of amyloid buildup.[7][18]
Once the tissue sample is collected, it is tested to determine the exact type of amyloid protein causing the disease. This step is crucial because different types of amyloidosis require different treatments. Identifying whether you have AL, AA, or ATTR amyloidosis, for example, helps your doctor choose the most effective treatment plan for you.[7][18]
Imaging Tests
Imaging tests allow doctors to see inside your body and assess how amyloidosis is affecting your organs. These tests can reveal structural changes, measure organ function, and help guide treatment decisions.[7][18]
An echocardiogram is one of the most commonly used imaging tests for amyloidosis. This test uses sound waves to create moving pictures of your heart, showing how well it is pumping blood and whether there are any structural abnormalities. Because amyloidosis often affects the heart, an echocardiogram can reveal thickening of the heart walls or other signs of cardiac amyloidosis.[7][18]
Magnetic resonance imaging (MRI) is another valuable tool. MRI uses radio waves and a strong magnetic field to create detailed images of your organs and tissues. It is particularly useful for examining the heart and can help doctors understand the structure and function of the heart muscle. MRI can also detect early signs of heart damage caused by amyloid deposits.[7][18]
Nuclear imaging, also called a nuclear scan, involves injecting tiny amounts of radioactive material into a vein. This material, known as a tracer, travels through your body and collects in areas where amyloid deposits are present. A special camera then takes pictures that show where the tracer has accumulated. Nuclear imaging is especially helpful for diagnosing cardiac amyloidosis and can sometimes distinguish between different types of the disease, which is important for planning treatment.[7][18]
Other imaging tests, such as computed tomography (CT) scans, may be used to examine organs like the liver, spleen, or kidneys. These scans provide cross-sectional images of the body and can show whether organs are enlarged or damaged.[7][18]
Additional Tests for Specific Types
If doctors suspect hereditary amyloidosis, they may recommend genetic testing. This involves analyzing your DNA to look for mutations in genes that produce abnormal amyloid proteins. Genetic testing can confirm whether you have an inherited form of the disease and can also help identify family members who may be at risk.[6][16]
For people with symptoms affecting the nervous system, such as numbness, tingling, or pain in the hands and feet, doctors may perform tests to assess nerve function. These tests can help determine whether amyloid deposits are affecting the nerves and causing neuropathy.[2]
Diagnostics for Clinical Trial Qualification
Clinical trials are research studies that test new treatments or approaches to managing amyloidosis. If you are considering joining a clinical trial, you will need to undergo specific diagnostic tests to determine whether you qualify. These tests help researchers ensure that participants meet certain criteria and that the trial is appropriate for their condition.[9]
The qualification process for clinical trials typically involves many of the same diagnostic tests used to diagnose amyloidosis in the first place. However, trials may have additional or more detailed requirements to ensure that participants are suitable for the experimental treatment being studied.[9]
Hematologic Testing
For trials focused on AL amyloidosis, researchers need to confirm the presence of abnormal light chain proteins. This is done through blood and urine tests that measure the levels of these proteins. A key test is the serum free light chain (FLC) assay, which measures the difference between involved and uninvolved light chains. Trials often require that this difference be above a certain threshold to confirm active disease.[9]
Some trials also require a bone marrow biopsy to confirm that there is an abnormal growth of plasma cells producing the light chain proteins. This helps researchers understand the underlying cause of the amyloidosis and tailor the treatment accordingly.[9]
Organ Function Assessment
Clinical trials need to know how well your organs are functioning before you begin treatment. This is important both for determining whether the trial is safe for you and for measuring how the treatment affects your organs over time.[9][12]
For heart function, trials commonly use an echocardiogram to measure your heart’s pumping ability, often expressed as the left ventricular ejection fraction (LVEF). Many trials require that your LVEF be above a certain level, such as 40%, to ensure your heart is strong enough to tolerate the treatment. Blood tests may also measure levels of specific markers like troponin or N-terminal pro-B-type natriuretic peptide (NT-proBNP), which indicate heart stress or damage.[9][12]
Kidney function is assessed through blood tests that measure estimated glomerular filtration rate (eGFR) and urine tests that check for protein loss. Trials may require that your eGFR be above a certain level, such as 30 mL/min per 1.73 square meters, although some trials accept participants on dialysis if they otherwise meet the criteria.[12]
Liver function tests measure enzymes and bilirubin levels in your blood. Trials often set limits on these values to ensure that your liver can handle the medications being tested. For example, direct bilirubin levels may need to be below 2 mg/dL.[12]
Lung function is evaluated through tests that measure oxygen saturation and the ability of your lungs to transfer gases. These may include a test called diffusing capacity of the lungs for carbon monoxide (DLCO), which should typically be above 50% of the predicted value for your age and size.[12]
General Health and Performance Status
Clinical trials often require that participants be in reasonably good overall health, aside from the amyloidosis itself. Doctors assess this using tools like the Eastern Cooperative Oncology Group (ECOG) performance status, which rates your ability to carry out daily activities on a scale from 0 to 4. Most trials require a performance status of 0 to 2, meaning you are able to take care of yourself and spend at least half of your waking hours out of bed.[12]
Blood pressure is another important factor. Trials may require that your blood pressure be stable and above a certain level, such as a systolic blood pressure greater than 90 mm Hg, to ensure you can tolerate the treatment without dangerous drops in blood pressure.[12]
Age and Other Criteria
Many clinical trials for amyloidosis have age limits, typically accepting participants between 18 and 70 years old. However, this varies depending on the trial. Some trials may also exclude people with certain other health conditions, such as active infections, other types of cancer, or severe heart failure.[12]
If you are interested in participating in a clinical trial, your doctor can help you understand the specific requirements and whether you are a good candidate. Clinical trials can offer access to new treatments that are not yet widely available and contribute to research that may help others with amyloidosis in the future.[9][12]
