Paraneoplastic Syndrome: Common Types and Symptoms

Paraneoplastic syndromes are a set of symptoms that occur with cancer that are due to substances a tumor secretes or due to the body's response to the tumor. They are most common with cancers of the lung, breast, ovary, and lymphomas, and may sometimes cause the first symptoms of the disease. The symptoms vary widely depending on the particular substances responsible and may include symptoms of high calcium, symptoms of a low sodium level in the blood, symptoms related to a high cortisol level (Cushing's syndrome), and others. Treatment usually focuses on treating the underlying cancer while managing the symptoms, such as high calcium.

Paraneoplastic Syndromes in Cancer

Paraneoplastic syndromes are considered rare, but some forms are more common than others, such as the paraneoplastic neuropathies, which may occur in around 10% of people with some cancers of the immunological system.

Cancers most commonly associated with paraneoplastic syndromes include lung cancer, breast cancer, ovarian cancer, pancreatic cancer, stomach cancer, kidney cancer, leukemias, and lymphomas.

When found with lung cancer, they most commonly occur with squamous cell and small cell lung cancer. The symptoms can involve virtually any body system and include symptoms that are not ordinarily associated with cancer. Symptoms from these syndromes may be the first sign that a cancer is present, arising well before symptoms of the cancer itself. Unfortunately, the symptoms can easily be misdiagnosed early on, especially if a diagnosis of cancer is not suspected.

In some cases, the tumor directly secretes the substance responsible for symptoms. In others, the body (immune system) produces the substance, often making the substance in an attempt to attack the tumor. When the substance damages healthy cells in addition to the tumor, it is a form of autoimmune response.

Paraneoplastic syndromes are not related to the size of a tumor or the presence of metastases and may occur before a tumor is diagnosed and even after a tumor has been removed.

Common Paraneoplastic Syndromes

There are several paraneoplastic symptoms seen with lung cancer, but the two most common include hypercalcemia and SIADH.

Hypercalcemia

Hypercalcemia as a paraneoplastic syndrome occurs most commonly with squamous cell carcinoma of the lungs, a form of non-small cell lung cancer. Hypercalcemia refers to an elevated level of calcium in the blood. Hypercalcemia with lung cancer can be caused by a combination of the cancer secreting a hormone known as parathyroid hormone-related peptide (PTHrP), plus calcium that is released by the breakdown of bone due to cancer being present in the bone.

Symptoms can include thirst, muscle weakness, loss of appetite, confusion, abdominal pain, and depression. The best way to treat hypercalcemia is by treating the cancer itself, but making sure people get enough fluids is very important both for the symptoms, and because this syndrome often causes serious kidney damage. When hypercalcemia is severe, other treatments are needed as well.

Syndrome of Inappropriate ADH Secretion (SIADH)

Syndrome of inappropriate ADH secretion or SIADH, occurs most commonly with small cell lung cancer, and is characterized by a low level of sodium in the blood (hyponatremia). Symptoms can include headaches, muscle weakness, memory loss, and fatigue, but if it occurs very fast or is very severe, it can cause seizures and loss of consciousness. The best way to treat SIADH is to treat the cancer, and one study found that treating small cell lung cancer with chemotherapy could reduce the symptoms of SIADH in up to 80% of people. Specific treatments for hyponatremia (low sodium) due to SIADH may include restricting water intake or using other fluids or medications.

Another paraneoplastic syndrome found in some people with lung cancer, called hyponatremia of malignancy, has a different mechanism but also involves low sodium levels in the blood.

Other Types

Paraneoplastic syndromes can affect nearly any region of the body and cause many different symptoms. Some of the more common syndromes involve the brain, endocrine system, skin, kidneys, eyes, bones, and blood cells. Since these symptoms may occur before lung cancer is diagnosed, it can be very frustrating as doctors look for the causes. A few other relatively common syndromes are listed here.

Cushing's Syndrome

Cushing's syndrome, a syndrome caused by elevated levels of cortisol in the blood, can cause swelling (often leading to a "moon-faced" appearance), high blood pressure, and stretch marks similar to those that some women acquire during pregnancy.

Acromegaly

In this syndrome, a lung tumor makes a hormone similar to growth hormone. While in children this might result in generalized growth, in adults it results primarily in growth of the hands and feet.

Hypoglycemia

Some lung tumors secrete substances that lower blood sugar levels. This can result in symptoms of hypoglycemia (low blood sugar) such as lightheadedness, tingling around the mouth, shakiness, hunger, and anxiety. When severe, confusion and loss of consciousness may occur.

Carcinoid Syndrome

Some lung cancers, as well as some carcinoid tumors of the lung (neuroendocrine tumors) secrete peptides such as serotonin that can cause facial flushing and diarrhea.

Polymyositis/Dermatomyositis

Some lung tumors secrete substances that result in inflammation of the skin and soft tissues (polymyositis/dermatomyositis). This is most common with squamous cell lung cancer.

Neurological Syndromes

There are several neurological syndromes that can represent paraneoplastic syndromes with lung cancer, with one example being cerebellar ataxia, a condition in which inflammation of the brain results in lack of coordination.

Paraneoplastic Glomerulopathy

Some lung tumors secrete substances that cause kidney damage, with paraneoplastic glomerulopathy being one example.

Treatments

Paraneoplastic syndromes vary widely in their symptoms, and there may even be several causes of one of these specific syndromes. For that reason, treatment will need to be tailored for each individual cancer and syndrome.

Overall, the best treatment for any of these syndromes (especially since the substances causing these symptoms are usually produced by cancer cells or by the body in reaction to cancer cells) is treating ​the underlying cancer.

When a substance is produced by the immune system (autoimmune response), treatments such as corticosteroids or other treatments to decrease the immune response may be needed.

Thankfully, treatments for lung cancer, even advanced lung cancer, have improved in the last few years, and progress is being made even in the more difficult-to-treat cancers, such as squamous cell carcinoma of the lungs and small cell lung cancer.

Prognosis

In general, lung cancers that are associated with paraneoplastic syndromes have a poorer prognosis, but this can vary depending on the specific syndrome as well as the type of lung cancer.

A Word From Verywell

Learning that your symptoms are due to a paraneoplastic syndrome can be very disconcerting, not only because they are associated with an underlying cancer, but because many people have not previously heard about these sometimes strange-appearing symptoms. It's particularly important to be your own advocate if you are coping with a paraneoplastic syndrome.

When diagnosed with cancer, it's sometimes far too easy to dismiss symptoms as being due to the cancer or a related syndrome, especially symptoms such as cancer fatigue.

Yet bringing all of your symptoms to the attention of your oncologist gives them the opportunity to look for other conditions that may be present and treatable, as well as to support you in managing the symptoms that cannot be alleviated.