What are the other Names for this Condition? (Also known as/Synonyms)

• Amyloidosis-Associated Pancreatic Disease
• Amyloidosis of Pancreas
• Pancreatic Islet Cell Amyloidosis

What is Pancreatic Amyloidosis? (Definition/Background Information)

• Amyloidosis is a group of disorders in which the ‘amyloid protein’ builds up in many organs and tissues of the body. The term “amyloid” is used for protein molecules of any type that stick together owing to misfolding (or incorrect formation of the proteins)
• These protein aggregates are abnormally-formed and arranged into fibrils (slender fibers). An amyloid build-up can occur locally in only one organ, or may occur throughout the body. When the amyloid proteins get deposited in the pancreas, the resulting condition is known as Pancreatic Amyloidosis
• Pancreatic Amyloidosis is an extremely rare type that typically affects older men and women. There are 5 major types of amyloidosis including amyloid light amyloidosis, AA amyloidosis, hereditary amyloidosis, wild-type ATTR amyloidosis, and dialysis-related amyloidosis
• Pancreatic Amyloidosis may occur as a manifestation of systemic AL amyloidosis, or as localized amyloidosis due to type-2 diabetes. The amyloid proteins can be found in both the endocrine and exocrine cells of the organ
• The condition may not manifest itself in the initial stages. With time, symptoms of type-2 diabetes may be experienced, which may include frequent infections, increased thirst and hunger, increased urination and blurred vision, among others
• Good glycemic control can help an individual manage Pancreatic Amyloidosis. However, if the pancreas are affected as part of systemic AL Amyloidosis with involvement of other major organs; then, the prognosis is more guarded and unfavorable

Who gets Pancreatic Amyloidosis? (Age and Sex Distribution)

• Pancreatic Amyloidosis is an extremely rare condition that may affect individuals with type 2 diabetes or systemic AL amyloidosis
• Although all age groups are vulnerable, Pancreatic Amyloidosis affects older adults more frequently. Both male and female genders may be affected
• The disorder is known to occur worldwide and no racial or ethnic bias is observed

What are the Risk Factors for Pancreatic Amyloidosis? (Predisposing Factors)

The following are some known risk factors for developing Pancreatic Amyloidosis:

• Advancing age
• A family history of amyloidosis
• Poorly-controlled diabetes
• AL amyloidosis, which arises from production of abnormal immunoglobulin in the bone marrow. The following conditions may predispose an individual to AL amyloidosis:
  • Benign monoclonal gammopathy
  • Malignant lymphoma
  • Multiple myeloma

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pancreatic Amyloidosis? (Etiology)

• Pancreatic Amyloidosis is caused by abnormal amyloid protein deposit, as a manifestation of systemic AL amyloidosis
• In localized amyloidosis involving the pancreas, individuals are known to have type 2 diabetes

When Pancreatic Amyloidosis occurs in systemic AL amyloidosis:

• The abnormal immunoglobulin light chain protein misfolding results in amyloid protein formation
• The amyloid protein fibrils circulate in the bloodstream and get deposited in the pancreatic cells
• The amyloid deposits in beta cells may cause type-2 diabetes

When Pancreatic Amyloidosis is localized and occurs due to type-2 diabetes:

• A major component of the amyloid protein is “islet amyloid polypeptide (IAPP)”
• IAPP is co-secreted in islet beta cells with insulin
• In type-2 diabetes, IAPP aggregates to form amyloid protein
• These amyloid proteins do not circulate in blood

What are the Signs and Symptoms of Pancreatic Amyloidosis?

The signs and symptoms of Pancreatic Amyloidosis may not be present in the initial stages of the condition. However, as the amyloid deposits increase, symptoms may become apparent and may include:

• Upper abdominal pain
• Enlarged pancreas
• Difficulty in breathing

Systemic AL amyloidosis associated Pancreatic Amyloidosis may lead to type-2 diabetes; or, type-2 diabetes may lead to localized Pancreatic Amyloidosis. In both cases, the affected individuals may exhibit signs and symptoms of type-2 diabetes such as the following:

• Bladder, kidney, skin, or other infections that are more frequent and/or heal slowly

• Fatigue
• Increased hunger and thirst
• Increased urination
• Blurred vision: If blood sugar becomes too high, it is possible for fluid to be pulled from the eye lenses, thus affecting the eye’s ability to focus clearly
• Erectile dysfunction
• Headaches
• Unexplainable weight loss
• Pain or numbing of the feet and hands
• Loss of consciousness (rare)
• Slow-healing of sores
• Itchy skin, usually around vaginal or groin area
• Frequent yeast infections
• Recent weight gain
• Velvety dark skin changes of neck, armpit, and groin, known as acanthosis nigricans
• Numbness and tingling of hands or feet

How is Pancreatic Amyloidosis Diagnosed?

The diagnosis of Pancreatic Amyloidosis may include tests to ascertain AL amyloidosis, as well as specific tests to assess damage to pancreas’ structure and function; and damage to other organs in systemic Amyloidosis.

The following methods may be employed for an accurate diagnosis of Pancreatic Amyloidosis:

• A thorough physical examination
• Evaluation of personal and family medical history
• Assessment of the presenting signs and symptoms
• Blood tests:
  • To obtain a complete blood count (CBC)
  • To assess abnormal antibodies
  • To check heart function (cardiac biomarkers for stress on the heart)
  • To perform “Freelite assay”, a measurement of light chain immunoglobulins
  • For measuring immunoglobulin by immunofixation electrophoresis
  • To measure levels of an enzyme known as alkaline phosphatase
• Urine tests:
  • To check for excess protein (a 24 hour urine test is usually performed)
  • To measure immunoglobulin by immunofixation electrophoresis
• Electrocardiography and echocardiography for checking heart functions
• Imaging tests, to assess amyloid deposits in the body/organs, and to assess damage to the organs, tissues, and bones, which include:
  • X-rays
  • Ultrasound imaging
  • Computed tomography scanning
  • Magnetic resonance imaging
  • Serum amyloid protein (SAP) scintigraphy scan: In this procedure, a small amount of radiolabeled (radioactive iodine) SAP is introduced through injection into the body. After several hours, individuals are scanned with a whole body gamma scanner to check for amyloid deposits in the tissues and organs. Individuals undergoing this procedure ingest potassium iodide before and after the procedure, to prevent the thyroid glands from absorbing the radioactive iodine
• Tissue biopsy: A biopsy of an affected organ or tissue is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis. In case of Pancreatic Amyloidosis,
  • Amyloid deposit from affected tissue is detected using a staining procedure
  • When stained with Congo red stain, the amyloid protein deposits appear green under a special type of microscope (polarizing microscope)
• Bone marrow aspiration for checking the type of abnormal immunoglobulin light chains
• Molecular testing to check the type of proteins in amyloid deposits (AL or AA chains) through mass spectrophotometry

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pancreatic Amyloidosis?

The potential complications of Pancreatic Amyloidosis associated with systemic AL amyloidosis may include:

• Development of type-2 diabetes
• Calcification of pancreas

Following are the potential complications of long-term type-2 diabetes (often after several years):

• Eye problems, which include poorer eyesight, particularly at night, and sensitivity to light. Diabetic retinopathy, a condition in which blood vessels of the retina are damaged, is caused by type 2 diabetes. This condition can potentially cause blindness. Type 2 diabetes also increases the risk for other vision disorders such as cataract and glaucoma
• Nerve damage, also known as neuropathy, is a common complication with type 2 diabetes. Excess sugar builds up in the blood vessels causing pain, tingling, and loss of feeling to the affected limbs
• Nerve damage in the feet increases the risk of certain food complications. Feet and skin can acquire sores and infections causing pain and itching. In severe cases, the foot or leg may need to be removed/amputated
• Nerve damage can cause weakness or problems with urination. It may also make it more difficult for men to have an erection
• Diabetes makes it difficult for one to control their blood pressure and cholesterol, leading to possible heart attacks, stroke, and other complications
• Diabetes may cause one’s bone mineral density to lower, thus increasing the risk for developing osteoporosis
• Alzheimer’s disease can be caused by type 2 diabetes
• Elevated blood sugar has the potential to lead to kidney damage, a condition that is known as nephropathy. The condition can damage the filtering system of the kidneys, leading to kidney failure or kidney disease
• Infections of skin, female genital tract, and urinary tract are more common among individuals with diabetes
• When an individual has diabetes, their risk of heart attack is equivalent to an individual who has already experienced a heart attack. Both women and men with diabetes are at equal risk

How is Pancreatic Amyloidosis Treated?

The treatment options for Pancreatic Amyloidosis are geared towards preventing disease progression and providing relief to the affected individuals. The treatment measures may be specific to each affected individual and the following may be considered:

• Medications, taken orally or intravenously, including:
  • Alpha-glucosidase inhibitors (acarbose)
  • Biguanides (metformin)
  • Injectable medicines (comprising of exenatide, mitiglinide, pramlintide, sitagliptin, and saxagliptin
  • Meglitinides (including repaglinide and nateglinide)
  • Sulfonylureas (such as glimepiride, glyburide, and tolazamide)
  • Thiazolidinediones (including rosiglitazone and pioglitazone)
• Diet: Having frequent and small meals through the day, with reduced fat and sodium content
• Moderate exercise

Pancreatic Amyloidosis generally does not occur in isolation; it is often associated with involvement of many other organs as part of systemic amyloidosis. Therefore, additional treatments pertaining to the subtype of amyloidosis, such as AL amyloidosis, and its underlying cause are often necessary.

How can Pancreatic Amyloidosis be Prevented?

• Currently, there are no specific methods or guidelines to prevent Pancreatic Amyloidosis
• Seeking medical attention for pre-existing conditions, such as diabetes, which can lead to Pancreatic Amyloidosis is advisable
• Active research is currently being performed to explore the possibilities for treatment and prevention of such disorders

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Pancreatic Amyloidosis? (Outcomes/Resolutions)

• The prognosis for Pancreatic Amyloidosis may be determined by a number of factors, such as the cause, extent of the disorder at diagnosis, organs affected, overall health of the affected individual, and his/her response to treatment
• If an individual has diabetes-associated Pancreatic Amyloidosis, good glycemic control and adequate treatment may further control damage to the organ
• The prognosis in systemic AL amyloidosis associated Pancreatic Amyloidosis may be guarded, particularly if vital internal organs are involved

Additional and Relevant Useful Information for Pancreatic Amyloidosis:

• Approximately, 30 different proteins with a tendency to form amyloids have been identified. These are known as precursor proteins or amyloidogenic proteins
• The misfolding of proteins can occur due to a number of reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum