People who have syndrome of inappropriate antidiuretic hormone secretion (SIADH) produce excessive amounts of antidiuretic hormones. It leads to the body developing an imbalance of sodium and water.

The kidneys need this hormone in the correct amount to properly control the volume of water the body loses in urine.

Someone who does not eliminate the appropriate amount of fluid is at risk of developing abnormally low levels of sodium or other electrolytes in the blood (known as hyponatremia). Doctors may commonly encounter hyponatremia in the clinic. It is important to note that SIADH is an underlying cause of this condition that doctors might not always catch.

The body makes antidiuretic hormones (ADH) in the hypothalamus, the part of the brain responsible for keeping the body in a stable state. The pituitary gland then has the job of releasing the hormone from the base of the brain.

Read on to learn more about SIADH, including what causes it and the associated symptoms. This article also discusses how doctors diagnose and treat SIADH.

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SIADH typically occurs as a result of another disease in the body.

A protein, vasopressin 2, interacts with ADH to control the water balance in the body. A hereditary form of the condition exists where experts believe that mutations in vasopressin 2 receptors found in the kidney can affect the protein’s activity, leading to SIADH.

What is the most common cause?

Certain health conditions, especially those that affect the central nervous system (CNS), commonly cause SIADH. These can include:

All these conditions have the potential to lead to excessive ADH release from the pituitary gland.

Cancer is another common cause. Small cell lung cancer is the most common type that causes excessive release of ADH. But other cancer types can cause SIADH, including:

  • small cell carcinomas
  • head and neck cancers
  • olfactory neuroblastoma, a type of nasal cavity tumor

Medications

Additionally, several drugs can increase the release or the effect of ADH. For instance, the seizure medications carbamazepine and oxcarbazepine can increase sensitivity to ADH.

The authors of a 2017 study involving 198 people looked into the relationship between certain medications and SIADH. The researchers diagnosed drug-induced SIADH in 146 (73.7%) of the participants and SIADH resulting from other causes in 52 (26.3%) of them. Specifically, they found connections with 5 types of medications in most diagnoses where drugs caused SIADH. These include:

  • antidepressants, especially selective serotonin reuptake inhibitors (SSRIs)
  • anticonvulsants, especially carbamazepine
  • antipsychotic drugs
  • cytotoxic drugs, which doctors use to kill cancer cells
  • pain medications

Other causes

Some additional causes of SIADH include:

  • surgery, pain-relieving medications may play a role in this setting
  • lung conditions, especially pneumonia
  • hormone deficiency conditions, including underactive pituitary and underactive thyroid
  • HIV or AIDS diagnoses, where people with either condition commonly have hyponatremia, which may be due to SIADH

Taking hormone treatments may also cause SIADH. Examples include:

  • vasopressin to treat gastrointestinal bleeding
  • desmopressin as a therapy for bedwetting at night, hemophilia, or blood clotting disorders
  • oxytocin to induce labor

Symptoms can vary and depend on how low the blood sodium levels become or the extent of swelling in the brain.

Normal blood sodium levels are between 135 and 145 milliequivalents per liter (mEq/L).

Early signs of acute hyponatremia can occur when a person’s blood sodium level falls below 125–130 mEq/L. At this point, symptoms can include nausea, malaise, and vomiting.

Sharper falls in blood sodium levels can cause:

  • headache
  • lethargy
  • reduced alertness
  • seizures

If a person’s blood sodium level falls below 115–120 mEq/L, the consequences can be life threatening. They may stop breathing and fall into a coma.

In chronic hyponatremia, a person’s brain adapts so that they do not show any symptoms, despite having a blood sodium level below 120 mEq/L. However, they may experience:

  • nausea and vomiting, which affects around a third of people with chronic hyponatremia
  • gait disturbance
  • memory and cognitive problems
  • fatigue
  • dizziness
  • confusion
  • muscle cramps

People over 65 years old more commonly experience SIADH with no known cause. Having mild to moderate hyponatremia can be a risk factor for fractures, falls, and gait (walking) problems in this population.

Doctors can often miss the subtle signs and symptoms of mild and chronic hyponatremia when examining a person.

No gold standard test exists. However, doctors today still use the SIADH diagnostic criteria Schwartz and Bartter developed in 1967. These include the following components:

  • blood sodium levels below 135mEq/L
  • blood electrolyte-water balance, known as osmolality, below 275 mOsm/kg
  • urine sodium levels above 40 mEq/L
  • urine osmolality above 100 mOsm/kg
  • no evidence of volume depletion, which is a deficiency of fluid in the spaces outside of the cells of the body, so a person has normal skin elasticity and blood pressure within the normal range
  • no other causes of hyponatremia, such as adrenal insufficiency or underactive thyroid
  • restricting fluid restriction resolves the hyponatremia

Doctors may also carry out kidney function and blood sugar tests.

A 2016 study highlighted a lack of randomized controlled trial evidence for managing SIADH. The researchers said that most of the guidance and recommendations are based on clinical judgment as opposed to hard data.

Management of SIADH requires clinical skill, patience, and diligence.

Doctors tend to treat SIADH by first correcting a person’s sodium levels, aiming for more than 130 mEq/L, and then maintaining that level. If there is an underlying health condition, such as underactive thyroid or CNS infections, then the doctor will also treat it.

In people with mild to moderate symptoms, restricting oral intake of water to less than 800 mL/day may be beneficial. A healthcare professional can help someone manage fluid restrictions.

People with persistent hyponatremia may need to take oral salt tablets or receive intravenous saline. The addition of loop diuretics, like furosemide, can help reduce urine concentration and increase water excretion, particularly in people with much higher urine osmolality than blood osmolality (higher than 500 mOsm/kg).

Severe SIADH

If a person has severe SIADH symptoms, they may require immediate hypertonic (a solution of high salts and low water) saline infusion for the first few hours. Doctors will then monitor their sodium level and adjust accordingly.

In cases of severe persistent SIADH, doctors may prescribe vasopressin receptor antagonists like conivaptan (intravenously) or tolvaptan (orally). These medications help prevent water retention by blocking vasopressin 2 receptors and correcting hyponatremia.

However, one 2018 study warns about the risks of overcorrecting hyponatremia with the use of tolvaptan. The researchers specifically advise caution regarding medication dosage in people with very low levels of both blood sodium and blood urea nitrogen.

Potential complications of SIADH depend on how far a person’s blood sodium level falls. They can include:

  • headaches
  • muscle cramps
  • memory problems
  • tremors
  • depression

In more severe cases, a person may:

  • stop breathing
  • have seizures
  • experience hallucinations
  • fall into a coma

The condition can be life threatening in some people with severe disease.

A person’s outlook depends on many factors, including the underlying cause of SIADH as well as how and to what extent the associated hyponatremia has affected them.

If a person’s SIADH is due to medication use, they will usually make a fast and full recovery once they stop taking the drug.

Some people may develop CNS dysfunction due to hyponatremia, known as acute hyponatremic encephalopathy. This condition may be reversible, but some people may develop permanent neurological damage or die from it. Premenopausal women are at the highest risk of this happening.

People with chronic SIADH may not always experience symptoms and therefore, may not know they need to see a doctor.

That said, a person experiencing any of the above-listed symptoms or having any concerns surrounding fluid retention should make an appointment with their doctor as soon as possible.

The sooner a person receives treatment, the better their chances of a positive outcome.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) causes the pituitary to release too much antidiuretic hormone (ADH).

It can be a hereditary condition. Alternatively, it can result from an underlying health problem like cancer, a CNS disorder, or pneumonia, or medications like SSRIs, anticonvulsants, or antipsychotics.

Symptoms can include nausea, vomiting, lethargy, and cognitive problems, but some people do not experience any symptoms.

Doctors treat the condition by recommending restriction of water intake, increasing salt intake, and potentially prescribing a vasopressin receptor antagonist like tolvaptan.