SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)

The syndrome of inappropriate antidiuretic hormone production (SIADH) is a condition associated with an increased water retention in the body derived from excessive production of antidiuretic hormone (ADH).

SIADH syndrome is characterized by hyponatremia (low concentration of sodium in the blood) caused by the excess of renal water reabsorption that results in a reduced urine output (antidiuresis).

The body maintains a balance between the total amount of water and the concentration of sodium. Many organs participate in this regulation such as the kidneys, the thyroid, the pituitary gland or the adrenal glands. Specifically, the pituitary gland release a hormone called antidiuretic hormone (ADH) or arginine vasopressin when the body has too little water or there is a high concentration of sodium. ADH causes the kidneys to increase the water retention and decreases the urine output.

In SIADH, there is an excessive and inappropriate production of antidiuretic hormone (ADH). The kidneys overreact to the ADH, so the body retains excess water and the sodium concentration in the blood becomes diluted and falls to abnormal levels.

SIADH (syndrome of inappropriate antidiuretic hormone production) is considered a paraneoplastic syndrome. A paraneoplastic syndrome causes symptoms in patients with a cancerous tumor that are not directly related to the tumor invasion. The main types of cancer known to cause SIADH are:

• Small-cell lung cancer: It is the most common cause and more that 75% of neoplasm that results in SIADH are from this type
• Gastrointestinal cancer: Pancreatic cancer, duodenal cancer or stomach cancer
• Head and neck cancer
• Brain tumors
• Genitourinary cancer (bladder cancer, prostate cancer, ovarian cancer)
• Lymphoma (including Hodgkin's disease)
• Thymoma

However, some conditions not related to cancer may cause the disorder. The most common ones are:

• Pulmonary diseases: Pneumonia, tuberculosis, asthma, cystic fibrosis, etc.
• Central nervous system (CNS) disorders: Skull fractures, traumatic brain injury, psychosis, meningitis, encephalitis, stroke, etc.
• Other causes: HIV, after surgery, hypothyroidism, etc.

A variety of drugs such as antiepileptic, antipsychotic or antineoplastic drugs may also cause SIADH:

• Chlorpropamide
• Carbamazepine
• Cyclophosphamide
• Vincristine and vinblastine

Patients with SIADH may not experience any symptom in the early stages. When the symptoms appear, it is usually due to hyponatremia (low concentration of sodium in the blood).

If there is a mild or moderate hyponatremia (125-135 mEq/l), symptoms are vague and nonspecific:

• Fatigue
• Loss of appetite
• Nausea and vomiting
• Headache
• Gait instability

If there is a marked hyponatremia (< 125 mEq/l) the patient may experience:

• Agitation
• Irritability
• Confusion
• Delusions and hallucinations

In case of severe hyponatremia (< 115 mEq/l):

• Seizures
• Coma

SIADH may be considered in patients with hypoosmolar hyponatremia (sodium in the blood below 135 mEq/l with a low plasmatic osmolality).

Other findings that are useful for the diagnosis are:

• A low level of BUN (Blood Urea Nitrogen) and uric acid in the blood
• High urine osmolality (> 100 Osm/kg)
• A high concentration of sodium in urine (> 40mEq/l)

The SIADH diagnosis is based on the exclusion of other possible causes of hyponatremia.

A water loading ADH suppression test may be helpful to diagnose SIADH.

The treatment depends on the underlying cause. It is necessary to know the cause for a proper treatment. Sometimes it is due to a tumor that can be treated with radiotherapy or chemotherapy.

In addition, it is necessary a fluid restriction. All patients require a sharp restriction of daily water intake following the medical prescription.

Severe cases may require medication. The most used are:

• Demeclocycline: Blocks the action of antidiuretic hormone (ADH) in the kidney
• Vaptans: Increase water excretion without affecting sodium or potassium excretion. The most commonly used are conivaptan intravenously and tolvaptan for oral administration.

It is also available the administration intravenously of a hypertonic saline solution in case of suffering from brain swelling, seizures or coma.