Merck Manual

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Paraneoplastic Syndromes


Robert Peter Gale

, MD, PhD, DSC(hc), Imperial College London

Reviewed/Revised Oct 2022

Paraneoplastic (associated with cancer—see also Overview of Cancer Overview of Cancer A cancer is an abnormal growth of cells (usually derived from a single abnormal cell). The cells have lost normal control mechanisms and thus are able to multiply continuously, invade nearby... read more ) syndromes occur when a cancer causes unusual symptoms due to substances that circulate in the bloodstream. These substances may be hormones Endocrine Function The main function of endocrine glands is to secrete hormones directly into the bloodstream. Hormones are chemical substances that affect the activity of another part of the body (target site)... read more produced by the tumor or antibodies Antibodies One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more Antibodies produced by the immune system. They can affect the function of various tissues and organs and cause symptoms at sites distant from the tumor. Paraneoplastic syndromes may affect many different organ systems, including the nervous system and the endocrine (hormone) system, causing such problems as nervous system changes, low blood sugar, diarrhea, or high blood pressure.

About 20% of people with cancer develop a paraneoplastic syndrome. The most common cancers associated with paraneoplastic syndromes include

Diagnosis of the paraneoplastic syndrome often includes testing for the substance circulating in the bloodstream that causes the paraneoplastic syndrome. Treatment of a paraneoplastic syndrome initially involves treating the symptoms. Eventually, treating the underlying cancer is the best way to control a paraneoplastic syndrome.

General paraneoplastic syndromes

People with cancer often experience fever, night sweats, loss of appetite, and weight loss. The syndromes below are less common.

Digestive tract syndromes

Watery diarrhea may result from substances secreted by certain cancers. Certain tumors that involve the intestines may secrete a lot of protein into the stool, causing low protein levels in the bloodstream.

Endocrine syndromes

Small cell carcinoma of the lung may secrete a substance that stimulates the adrenal gland Overview of the Adrenal Glands The body has 2 adrenal glands, one near the top of each kidney. They are endocrine glands, which secrete hormones into the bloodstream. Each adrenal gland has 2 parts. Medulla: The inner part... read more to produce increased levels of the hormone cortisol, which can cause weakness, weight gain, and high blood pressure (Cushing syndrome Cushing Syndrome In Cushing syndrome, the level of corticosteroids is excessive, usually due to taking corticosteroid medications or overproduction by the adrenal glands. Cushing syndrome usually results from... read more Cushing Syndrome ). Small cell carcinoma of the lung may also produce vasopressin, causing water retention, decreased sodium levels, weakness, confusion, and seizures in some people.

Very high calcium levels Hypercalcemia (High Level of Calcium in the Blood) In hypercalcemia, the level of calcium in blood is too high. A high calcium level may result from a problem with the parathyroid glands, as well as from diet, cancer, or disorders affecting... read more Hypercalcemia (High Level of Calcium in the Blood) in the blood (hypercalcemic syndrome) may occur in people with solid tumors or leukemias. Hypercalcemic syndrome can occur when the cancer secretes into the blood a hormone-like substance (similar to parathyroid hormone) that causes release of calcium from bone. High calcium levels may also result if the cancer directly invades bone, thereby releasing calcium into the bloodstream. As a result of the high calcium levels in the blood, the person develops kidney failure and confusion, which can progress to coma and even death if not recognized and treated promptly.

Neurologic syndromes

Polyneuropathy Polyneuropathy Polyneuropathy is the simultaneous malfunction of many peripheral nerves throughout the body. Infections, toxins, drugs, cancers, nutritional deficiencies, diabetes, autoimmune disorders, and... read more is a dysfunction of peripheral nerves (nerves outside the brain and spinal cord), resulting in weakness, loss of sensation, and reduced reflexes. Subacute sensory neuropathy is a rare form of polyneuropathy that sometimes develops before the cancer is diagnosed. It causes a disabling loss of sensation and incoordination but little weakness. Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is a form of polyneuropathy causing muscle weakness, which usually worsens over a few days to weeks, then slowly improves or returns to normal on its own. With treatment... read more is another type of nerve dysfunction that causes a general loss of muscle strength. It is more common in people with Hodgkin lymphoma.

Subacute cerebellar degeneration occurs rarely in patients with breast cancer, ovarian cancer, small cell carcinoma of the lung, or other solid tumors. This disorder may be caused by an autoantibody (an antibody that attacks the body's own tissues) that destroys the cerebellum. Symptoms can include unsteadiness in walking, incoordination of the arms and legs, difficulty speaking, dizziness, and double vision. Symptoms may appear before the cancer is detected.

Uncontrollable eye movements (opsoclonus) and quick contractions of the arms and legs (myoclonus) can occur in some children with neuroblastoma.

Subacute motor neuronopathy occurs in some people with Hodgkin and non-Hodgkin lymphoma. The nerve cells of the spinal cord are affected, weakening the arms and legs.

A variety of unusual symptoms may result from antibodies directed against the tumor that also interact with brain tissue to cause a change in mental function, disorientation, vision changes, and muscle weakness.

Eaton-Lambert syndrome Eaton-Lambert Syndrome Eaton-Lambert syndrome is an autoimmune disorder that impairs communication between nerves and muscles, causing weakness. Eaton-Lambert syndrome usually precedes, occurs with, or develops after... read more occurs in some people with small cell carcinoma of the lung. This syndrome is characterized by extreme muscle weakness caused by lack of proper activation of the muscle by the nerve.

Subacute necrotizing myelopathy is a rare syndrome in which rapid loss of neurons in the spinal cord leads to paralysis.

Skin syndromes

Itching is the most common skin symptom people with cancer have. Flushing is also common.

Other syndromes

Polymyositis Autoimmune Myositis Autoimmune myositis causes inflammation and weakness in the muscles (polymyositis) or in the skin and muscles (dermatomyositis). Muscle damage may cause muscle pain and muscle weakness may cause... read more Autoimmune Myositis is muscle weakness and soreness resulting from muscle inflammation. When polymyositis is accompanied by skin inflammation, the condition is called dermatomyositis.

Hypertrophic osteoarthropathy can occur in people with lung cancer. This syndrome alters the shape of the fingers and toes and can cause painful swelling of some joints.

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