Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

How SIADH works

ADH is made in the hypothalamus and released by the pituitary gland. Normally, it is released when blood becomes too concentrated or blood volume falls, and it tells the kidneys to reabsorb water. When the blood becomes dilute, ADH switches off and you pass large amounts of dilute urine.

In SIADH, ADH keeps being released (or acts on the kidney) even though the blood is already dilute. The kidneys keep concentrating urine and holding water. Total body water rises slightly but not enough to cause visible swelling, so people appear to have normal fluid levels (euvolemic). The result is dilutional hyponatremia. It is one of the most common causes of low sodium in hospital patients.

Causes of SIADH

Sometimes no cause is found, particularly in older people. A search for an underlying cancer is considered when SIADH is unexplained.

Symptoms

Symptoms depend on how low the sodium is and how fast it fell. The brain swells when blood becomes dilute quickly.

Even "mild" chronic hyponatremia from SIADH is linked to unsteady gait, slower reactions, falls and fractures in older adults.

Diagnosis

SIADH is a diagnosis of exclusion. Doctors confirm:

1. Low serum sodium (below 135 mmol/L) and low serum osmolality (below 275 mOsm/kg).
2. Inappropriately concentrated urine: urine osmolality above 100 mOsm/kg.
3. High urine sodium: usually above 30 to 40 mmol/L on a normal salt intake.
4. Normal fluid status: no signs of dehydration or of fluid overload such as heart failure, cirrhosis or kidney disease.
5. Normal thyroid and adrenal function: hypothyroidism and cortisol deficiency (including Addison's disease and pituitary problems) must be ruled out.
6. No recent diuretic use, especially thiazides.

A chest X-ray or CT, brain imaging and a review of all medicines help identify the cause.

SIADH vs other causes of low sodium

• Cerebral salt wasting: after brain injury, the kidneys lose salt and the person becomes dehydrated. Treatment is salt and fluid, the opposite of SIADH.
• Diabetes insipidus: the reverse problem, too little ADH action, causing large amounts of dilute urine and high sodium.
• Too much water intake or low solute intake: urine is very dilute, unlike SIADH.

Treatment

Emergency treatment for severe symptoms

Seizures, severe confusion or coma need hospital treatment with small boluses of hypertonic (3%) saline to raise sodium a few points quickly, with blood tests every few hours.

Correcting sodium safely

In chronic hyponatremia (present for more than 48 hours), the brain has adapted. Raising sodium too fast can cause osmotic demyelination syndrome, a severe brain injury that appears 2 to 6 days later with difficulty speaking and swallowing, weakness and behavior changes. Guidelines limit the rise to about 8 to 10 mmol/L in the first 24 hours, and less in high-risk people (alcohol use disorder, malnutrition, low potassium, liver disease).

Ongoing treatment

• Treat or remove the cause: stop or switch the responsible medicine, treat pneumonia or a brain infection, control pain and nausea.
• Fluid restriction: usually to about 800 to 1,000 mL (27 to 34 oz) a day, including all drinks, soup and ice. This is the first-line treatment for mild to moderate SIADH.
• Increasing solute intake: salt tablets with or without a loop diuretic, or oral urea, which helps the kidneys excrete water.
• Vaptans: tolvaptan blocks ADH at the kidney. It is started in hospital so sodium can be monitored, and is limited in duration because of liver risks.

Plain IV saline (0.9%) does not reliably raise sodium in SIADH and can lower it further, because the kidneys keep the water and excrete the salt.

Outlook

When SIADH is caused by a drug, surgery or infection, it usually resolves within days to weeks after the trigger is removed. SIADH caused by cancer or chronic brain conditions may be long-term and needs ongoing fluid restriction or medicines. People with past drug-induced SIADH should avoid the same medicine and have sodium checked when starting similar drugs.

Frequently asked questions

What is the most common cause of SIADH?

In everyday practice, medicines are among the most common causes, especially SSRIs and SNRIs antidepressants, carbamazepine and oxcarbazepine. Pneumonia, brain conditions, surgery, pain and nausea are also frequent triggers. Small cell lung cancer is the most common cancer cause.

What are the symptoms of SIADH?

SIADH itself causes symptoms only through low sodium. Mild cases often have none. As sodium falls, people develop nausea, headache, tiredness, muscle cramps and unsteadiness, then confusion, drowsiness and seizures. Older adults may just fall more or seem forgetful.

Why is fluid restriction used for SIADH?

In SIADH, the kidneys cannot get rid of extra water because ADH keeps telling them to hold it. Drinking less water stops the blood from becoming more dilute and lets sodium rise gradually. Restriction usually means about 800 to 1,000 mL of total fluid a day.

What is the difference between SIADH and diabetes insipidus?

They are opposites. In SIADH, too much ADH causes water retention, concentrated urine and low sodium. In diabetes insipidus, too little ADH, or kidneys that ignore it, causes large volumes of dilute urine, thirst and a tendency to high sodium.

Why can't low sodium be corrected quickly?

When sodium has been low for more than about 2 days, brain cells adjust to the dilute blood. Raising sodium too fast pulls water out of these cells and can damage the protective coating of nerves, causing osmotic demyelination syndrome. Doctors raise sodium slowly and monitor it closely.