Syndrome of inappropriate antidiuretic hormone (SIADH)

Syndrome of inappropriate antidiuretic hormone (SIADH) is a group of symptoms that develop when there is too much antidiuretic hormone (ADH) in the body. ADH is released by the pituitary gland in the brain and plays an important role in balancing water and sodium levels in the body. It lowers the amount of urine your body makes by increasing the amount of water your kidneys hold. Too much ADH causes your body to retain too much water. This can lead to electrolyte imbalances and a low level of sodium in the blood (called hyponatremia or water intoxication).

Hyponatremia can affect how the brain, heart, nervous system and tissues work, making SIADH a serious health problem. An extremely low sodium level in the blood is an emergency and can be life-threatening.

Some cancers can cause SIADH because they produce and release ADH in addition to the pituitary gland, which leads to too much ADH in the body.

Cancers that produce ADH include:

• small cell lung cancer
• non–small cell lung cancer
• mesothelioma
• pancreatic cancer
• neuroendocrine tumours
• thymoma, which is a type of thymus cancer
• primary brain tumours (cancer that starts in the brain)
• head and neck cancers

Some cancer treatments can cause the body to inappropriately release ADH. These include chemotherapy drugs such as cyclophosphamide (Cytoxan, Procytox) and vincristine (Oncovin). Other medicines used in cancer treatment, including opioid pain medicines such as morphine, can also lead to SIADH.

SIADH may also be caused by:

• neurological problems such as a stroke or encephalitis (inflammation of the brain)

• lung diseases such as pneumonia or tuberculosis
• medicines such as diuretics, antidepressants, antiseizure drugs and antipsychotic drugs

Symptoms of SIADH depend on how low and how quickly the sodium level in your blood drops. Mild cases can show no symptoms. Symptoms usually appear and get worse as the sodium level goes down.

Symptoms of SIADH include:

• fatigue (extreme tiredness or lack of energy)
• loss of appetite
• headache
• nausea
• vomiting
• muscle cramps
• abnormal heart rhythm
• neurological symptoms such as numbness and tingling or feeling confused, irritable, agitated, combative, delirious or disoriented, or having hallucinations
• physical symptoms such as feeling weak or lethargic, or having poor balance
• seizures
• coma

Report symptoms to your doctor or healthcare team right away.

Diagnosing SIADH usually includes physical and neurological exams. Your doctor will ask questions about your symptoms and health history, and check your coordination and how well your muscles and reflexes are working. You may also need to have the following tests:

• Blood chemistry tests are done to check the sodium, blood urea nitrogen (BUN), creatinine, albumin and uric acid levels in the blood.

• Urine tests are done to check the level of sodium in the urine. The amount of sodium in the urine will be high if you have SIADH.

• Osmolality tests are done to measure the concentration of all the chemicals in the fluid part of the blood or in urine. These tests check the body’s water and electrolyte balance. With SIADH, blood osmolality will be low and urine osmolality will be greater than blood osmolality.

If test results show that the sodium level in your blood is low but your adrenal glands, thyroid, kidneys, heart and liver are working well, you may be diagnosed with SIADH.

If your doctor thinks that cancer may be causing SIADH, imaging tests such as a chest x-ray or CT scan may be done to see if there is evidence of tumours.

Find out more about these tests and procedures.

Once SIADH is diagnosed, your healthcare team will treat it. They will closely monitor your blood's sodium level, your kidney function and any neurological or cardiac symptoms. They will also suggest ways to increase your blood's low sodium level (hyponatremia). Managing hyponatremia depends on how severe it is and if it is acute (sodium level has dropped suddenly) or chronic (level has been low for some time).

For mild to moderate hyponatremia, you may only need to limit how much you drink until the sodium level returns to normal. This is commonly done for acute cases of hyponatremia. Chronic hyponatremia treatment may involve temporarily taking medicines such as tolvaptan (Samsca) to block the production of ADH.

Severe hyponatremia is an emergency that needs to be treated in a hospital. You may be given a saline (salt water) solution through a needle in a vein (intravenous, or IV) to increase your blood's sodium level. You may also be given medicine to increase the amount of urine your body produces.

If cancer is causing SIADH, treating the cancer may help stop SIADH from happening again in the future.