Paraneoplastic Syndromes in Small-Cell Lung Cancer

Medically Reviewed by Jennifer Robinson, MD on August 04, 2022
5 min read

Paraneoplastic syndromes are a group of symptoms that happen in some people who have small-cell lung cancer (SCLC). Some paraneoplastic syndromes affect your nervous system, including your brain, spinal cord, and nerves. Others affect your endocrine system (your hormone system).

They can be the first sign of cancer and may help your doctor detect it sooner. There’s no cure, but there are ways to ease symptoms. Here’s what you need to know.

Neurologic and endocrine paraneoplastic syndromes have different causes. In paraneoplastic neurologic syndrome, white cells and antibodies that normally fight cancer attack healthy nerve cells by mistake. This is called an autoimmune response. That means your symptoms aren’t caused by SCLC, but by your body’s immune system. This immune response may damage your nervous system more than it harms the tumor.

In paraneoplastic endocrine syndrome, tumors start to make their own hormones. Your body already makes these hormones, usually in the exact amount you need. This sometimes makes your cancer harder to diagnose and treat. Symptoms depend on the type of hormone, but most can have serious effects on your body.

Paraneoplastic neurologic syndrome can attack almost any part of your nervous system. It usually affects one area at a time but may strike different areas as the disease goes on. Symptoms can come on fast or more slowly and start before or during cancer. They include:

Limbic encephalitis. This is inflammation of the limbic system. That’s the part of the brain that manages memory, emotion, and behavior. The limbic system helps control your blood pressure, heart rate, hormones, sleep-wake cycle, and how much you eat and drink. With limbic encephalitis, you may have mood changes, trouble with sleep and short-term memory, and seizures.

Cerebellar degeneration. This can cause severe problems with balance and the muscles that help you see, speak, and swallow. In time, you may not be able to read, write, or take care of yourself. Cellular degeneration is one of the most disabling paraneoplastic neurologic conditions. It’s also one of the hardest to treat.

Encephalomyelitis. This can affect many parts of the brain and spinal cord and trigger a wide range of symptoms. In the early stages, encephalomyelitis can look a lot like Parkinson’s disease.

Opsoclonus-myoclonus. This is a problem with the part of the brain that affects your muscles and balance. It causes rapid eye movements and muscle twitches you can’t control.

Stiff-person syndrome. Once called stiff-man syndrome, this group of symptoms causes severe stiffness in the low back and legs as well as painful muscle spasms.

Lambert-Eaton myasthenic syndrome (LEMS). About 60% of people with SCLC have LEMS, though it's likely more people have it but haven’t been diagnosed. LEMS disrupts signals between your nerves and muscles and can lead to weak legs, fatigue, and trouble swallowing. Men with LEMS may struggle with sexual function.

Peripheral neuropathy. This is damage to the nerves that send signals from your brain and spinal cord to the rest of your body. You have two types of peripheral nerves – motor and sensory. Motor nerves help you move. Sensory nerves help you feel things like heat, cold, and pain. Peripheral neuropathy isn’t always the result of a paraneoplastic neurologic syndrome. Cancer and side effects of treatment can cause it, too.

Neuromyotonia (Isaacs’ syndrome). This is marked by problems with the nerves that control muscle movement outside your brain and spinal cord. You may have twitching, muscle cramps, and stiffness.

Dysautonomia. This is damage to nerves that control your heart rate, blood pressure, and bowels and bladder (your autonomic nervous system). Dysautonomia can trigger low blood pressure and an irregular heartbeat.

Hormones made by tumors are called ectopic hormones. This means they come from tissue that doesn’t usually make them. Symptoms may include:

Cushing syndrome. Too much of the stress hormone cortisol or steroid drugs like prednisone usually cause Cushing syndrome. In people with SCLC, the problem is a tumor that makes adrenocorticotropin (ACTH), a hormone that controls cortisol. Too much ACTH or cortisol can lead to fatty deposits in your face, around your belly, and between your shoulders. It can also cause muscle loss, easy bruising, and high blood pressure.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH). This happens when a tumor makes antidiuretic hormone (ADH), a hormone normally made by your pituitary gland. ADH controls the amount of water your kidneys reabsorb when they filter waste from your kidneys. Too much can cause symptoms that range from nausea and fatigue to seizures and coma.

Hypercalcemia. In hypercalcemia, the calcium level in your blood is higher than normal. It happens when a tumor makes a type of parathyroid hormone (parathyroid hormone-related peptide). Parathyroid hormone controls the amount of calcium in your bones and blood. Hypercalcemia can cause weakness, nausea, vomiting, and kidney failure. If not treated, it can be life-threatening.

Paraneoplastic syndromes can be hard to diagnose because they often cause symptoms that are common in cancer. And cancer and its treatments can cause symptoms that look a lot like one of these syndromes.

You’ll likely get some of these tests to help your doctor figure out what’s causing your symptoms:

  • Complete blood count (CBC)
  • Comprehensive metabolic panel
  • Urinalysis
  • Hormones that tumors make, such as ACTH and ADH
  • Analysis of the fluid around your brain and spinal cord (cerebrospinal fluid)

They’ll also test for antibodies in your blood and cerebrospinal fluid. Antibodies are the protective proteins your immune system makes to help fight cancer. In paraneoplastic syndromes, they also attack healthy cells. Not everyone with a neurologic paraneoplastic syndrome has antibodies. But if they’re present, it’s a good sign you have the syndrome. Antibodies may also help your doctor pinpoint the type of cancer. For example, many people with SCLC have what are known as Hu antibodies in their brain and spinal cord fluid.

If your doctor suspects cancer, you may have imaging tests to help locate it, such as:

  • A CT scan of your chest, belly, and pelvis
  • Ultrasound, a test that uses sound waves to show images inside your body
  • A PET scan, often combined with CT scan or an MRI

If you have SCLC, the first and most important step is to treat it. The goal is to get rid of the cancer as well as the paraneoplastic syndrome. Unfortunately, syndrome symptoms, especially those that affect your nervous system, don’t always go away when the tumor’s removed. Your doctor may try other treatments, such as:

  • Corticosteroids like prednisone to lower inflammation
  • Immunosuppressants like azathioprine (Imuran) and rituximab (Rituxan) to slow your immune response
  • Intravenous immunoglobulin that delivers healthy antibodies through a vein to destroy antibodies causing the syndrome