Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a condition in which there are high amounts of antidiuretic hormone (ADH) released from the pituitary gland or other sources.
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SIADH often leads to low levels of sodium in the blood (hyponatremia), high urine osmolality and excessive sodium in the urine, and low serum osmolality. It is the most common cause of hyponatremia.
There are four types of SIADH: type A, B, C, and D.
Type A occurs independently of plasma osmolality. There are high levels of ADH and urine osmolality.
Type B is characterized by a constant release of ADH.
Type C is characterized by a baseline plasma sodium concentration that is stable, but lower than normal.
Type D shows normal ADH levels but high urine osmolality.
The Role of Antidiuretic Hormone in the Body
Antidiuretic hormone is also called arginine vasopressin (AVP). It is produced in the hypothalamus in the brain.
ADH has been found to help to regulate the osmotic balance in the body, which refers to the amounts of electrolytes and non-electrolytes in the cells, tissues, and interstitial fluid.
It also regulates sodium levels, blood pressure, and helps the kidneys to function normally.
ADH is also responsible for regulating water retention in the body. The more ADH there is the body, the more water will be retained. Conversely, less water will be retained if ADH levels are low.
Mechanism of SIADH
The mechanism by which SIADH develops primarily involves the kidneys. Inside the kidneys are tubes called nephrons that move fluid and waste along to the bladder and control how much water leaves the body. Fluids and electrolytes can pass through the nephrons to be released into the blood if necessary.
ADH affects two particular areas of the nephrons, called the distal convoluted tubules and the collecting ducts. These tubes reabsorb water back into the blood and are lined with proteins called aquaporins that allow water to move in and out of the cells that make up the distal convoluted tubule and the collecting ducts.
When there are low ADH levels, less aquaporins are lining the walls of the nephrons, meaning that the water passes through the collecting ducts and distal convoluted tubules and leaves the body as dilute urine. High ADH levels mean that the aquaporins release the water back into the blood.
When water is released back into the blood, plasma osmolality drops, leading to the blood becoming diluted. This causes the pituitary gland to lower the amount of ADH being produced. As a result, there is a high amount of dilute urine produced, which brings the osmolality levels back to normal.
However, if ADH is still produced when the plasma osmolality is low, more water is retained and it continues to dilute the blood and the electrolytes in it, such as sodium.
Dilute blood also takes up more space in the blood vessels, which causes a hormone called aldosterone to get rid of sodium through the urine when there are already low levels of sodium.
This leads to symptoms of SIADH, which occur because of the low levels of sodium in the blood.
Causes of SIADH
Usually, SIADH occurs because of another disease. However, there is a range of causes of SIADH.
Central nervous system (CNS) problems
CNS disorders such as stroke, infections, trauma, hemorrhage, and psychosis all increase the amount of ADH released by the pituitary gland.
Cancer
Tumors in the lung, in particular small cell lung cancer (SCLC), may increase the ADH levels in some cases. Other cancers such as pancreatic cancer, duodenum cancer, and head and neck cancers can also produce ADH. Some cancer treatments can also cause SIADH.
Drugs
Certain types of drugs may cause SIADH. These drugs may include:
- Amphetamines
- Anti-convulsant drugs
- Anti-psychotic drugs
- Chemotherapy drugs
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Opiates
- Selective serotonin reuptake inhibitors (SSRIs).
Surgery
Abdominal and thoracic surgery can increase ADH, as well as surgery to the pituitary gland.
Lung disease
Lung disorders such as pneumonia, bronchial asthma, atelectasis, acute respiratory failure, and pneumothorax can cause SIADH, although the mechanisms through which this happens is not known.
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Hormone administration
A person may develop SIADH after being given certain hormones, such as vasopressin (which is simply ADH in drug form), desmopressin, or oxytocin. All of these drugs increase the activity of vasopressor-2 (V2) receptors in the kidneys.
Human Immunodeficiency Virus (HIV)
HIV may cause a person to be more susceptible to infections and malignant diseases, which can cause hyponatremia and SIADH. Acquired immune deficiency syndrome (AIDs) is also associated with SIADH.
Hereditary SIADH
Genetic syndromes such as nephrogenic syndrome and hypothalamic syndrome have been associated with SIADH. In nephrogenic syndrome, a gene mutation in the V2 receptor on the X chromosome, which is responsible for the reabsorption of water in the collecting ducts, is linked to SIADH.
In hypothalamic syndrome, a mutation in the transient receptor potential vanilloid type 4 (TRPV4) has been linked to SIADH. The body’s ability to sense hypo-osmolality is impaired with hypothalamic syndrome, so ADH production may not be slowed.
Symptoms of SIADH
The symptoms of SIADH are caused by the loss of sodium in the blood.
- The symptoms can include:
- Nausea and vomiting
- Muscle cramps or tremors
- Low mood
- Memory problems
- Irritability
- Personality changes including combativeness, confusion, and hallucinations
- Seizures
- Coma.
Diagnosis of SIADH
A set of criteria was created in 1967 by William Schwartz and Frederic Bartter for the diagnosis of SIADH that are still in use today. These criteria are:
- Serum sodium less than 135mEq/L
- Serum osmolality less than 275 mOsm/kg
- Urine sodium over 40 mEq/L
- Urine osmolality over 100 mOsm/kg
- No evidence of volume depletion
- No evidence of other causes of low sodium levels, such as hyperthyroidism, cardiac failure, kidney disease, or pituitary gland problems
- Sodium levels improve with fluid restriction.
Treatment for SIADH
The type of treatment a person receives depends on the severity of their symptoms, along with their overall health, age, and any other existing conditions they may have.
Those with mild to moderate symptoms will be asked to restrict their oral water intake to under 800 milliliters a day. For chronic hyponatremia, oral salt tablets can help to increase the sodium levels in the body, or intravenous saline can be administered. Loop diuretics used with salt tablets can help to decrease urine concentration and increase water excretion.
If a person has chronic SIADH, they may need to restrict their fluid and water intake permanently.
Medication can be used to treat SIADH, including medications that reduce the production of ADH, and medications that regulate body fluid volume.
Surgical options include removing tumors that may be producing ADH.
Summary
Syndrome of inappropriate antidiuretic hormone secretion causes low sodium levels in the blood through excessive water retention. The extra water diluting the blood lowers the amounts of certain electrolytes in the blood and can cause serious symptoms such as seizures, coma, and psychological symptoms such as mood changes and hallucinations.
Sodium levels can be brought back to their normal rates by restricting the amount of water or fluid a person takes in, which may be a permanent solution if sodium levels are chronically low.
Although SIADH can be inherited, it is usually caused by an underlying disease, which should be treated along with SIADH.
Further Reading