Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a condition in which the body makes too much antidiuretic hormone (ADH). ADH, also known as vasopressin, helps regulate how much water your body loses through urine.
If too much vasopressin is made, your body will retain excessive amounts of water, diluting the concentration of sodium in your blood and leading to a potentially serious condition known as hyponatremia. When hyponatremia is severe, it can lead to nausea, loss of balance, seizures, and even death.
SIADH can be caused by conditions affecting parts of the central nervous system, certain medications, lung diseases, and cancers. The treatment varies by the underlying cause.
Klaus Vedfelt / Getty Images
What Does ADH (Vasopressin) Do in the Body?
Vasopressin is a hormone created in a part of the brain called the hypothalamus, which is then transferred and secreted by the pituitary gland (also known as the master gland).
Vasopressin has two functions in the body:
- Vasopressin causes water to be reabsorbed in the kidneys and returned to circulation, maintaining the ideal volume of water in the body and the ideal concentration of electrolytes (electrically charged minerals) like sodium.
- Vasopressin causes the constriction (narrowing) of small blood vessels known as arterioles, helping raise the blood pressure whenever it drops.
Vasopressin secretion may be triggered by hypotension (low blood pressure), hypovolemia (low water or blood levels), or disruptions in plasma osmolality (the balance of water and electrolytes in the body).
Vasopressin is important because it helps the body maintain homeostasis (a stable and balanced state) so it can function normally.
Hormone and Electrolyte Imbalances in SIADH
SIADH most commonly occurs when a disease, infection, other medical condition, or drug causes the excessive release of vasopressin. When this happens, it sets off the following chain reaction that can affect multiple organ systems:
- The inappropriate release of vasopressin returns water from the kidneys’ filtering units (called nephrons) back into the body, diluting electrolytes that help the body function.
- The drop in electrolyte concentrations alters osmosis (the passage of water between membranes), causing cells to take in more and more water. As the cells become overloaded with water, they can malfunction, sometimes severely. This affects all cells.
Sodium is the electrolyte of main concern as it is central to the regulation of blood pressure and blood volume. When sodium concentrations are abnormally low, you are said to have hyponatremia. Depending on how low sodium concentrations are, symptoms can range from mild to life-threatening.
With SIADH, hyponatremia may either be acute (sudden and/or severe) or chronic (persistent), depending on the underlying cause.
Causes of SIADH
SIADH may be caused by disruption of the central nervous system, which regulates vasopressin production (referred to as primary SIADH). It may also be caused by a disease or condition that adversely affects either the central nervous system or vasopressin receptors in the kidneys (referred to as secondary SIADH).
The most common causes of SIADH (by order of frequency) are:
Cancer
Cancer, a secondary cause of SIADH, accounts for around 24% of cases.
Certain cancers can cause paraneoplastic syndrome, a condition in which the body’s immune system inappropriately attacks the brain, causing the overstimulation of the hypothalamus and the overproduction of vasopressin.
This is most commonly seen with cancers like:
Medications
Medications are another secondary cause of SIADH, accounting for roughly 18% of cases. Some drugs cause SIADH by overstimulating the hypothalamus or pituitary gland, while others amplify the effects of vasopressin or activate vasopressin receptors in the absence of vasopressin.
Some of the most common drug culprits include:
- Anticonvulsant drugs like Depakote (valproic acid), Tegretol (carbamazepine), and Trileptal (oxcarbazepine)
- Atromid-S (clofibrate), a cholesterol-lowering drug known as a fibrate
- Chemotherapy drugs like Cytoxen (cyclophosphamide), Ifex (ifosfamide), and Oncovin (vincristine)
- Compazine (phenothiazine), an antipsychotic and migraine drug
- Diabinese (chlorpropamide), an anti-diabetes drug
- Elavil (amitriptyline), a tricyclic antidepressant also used for chronic pain
- MDMA (3,4-Methylenedioxymethamphetamine), also known as ecstasy
- Opioid painkillers like morphine and oxycodone
- Selective serotonin reuptake inhibitor (SSRI) antidepressants, especially Celexa (citalopram)
Central Nervous System Disorders
Central nervous system disorders account for around 9% of SIADH cases. These primary causes of SIADH directly affect the hypothalamus and/or pituitary gland.
Causes of primary SIADH include:
Even mental illnesses, such as psychosis, can overstimulate parts of the brain and trigger the inappropriate release of vasopressin.
Other Causes
Several other conditions can cause secondary SIADH (also known as acquired SIADH).
These include lung diseases like asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD), or lung infections like pneumonia and pulmonary abscess. Even so, the exact relationship between these conditions and SIADH is largely unknown.
SIADH can also be inherited due to a genetic mutation of the X chromosome. This rare condition, also known as nephrogenic SIADH, causes vasopressin receptors in the kidneys to activate even in the absence of vasopressin. Nephrogenic SIADH is characterized by chronic fluid retention and chronic hyponatremia.
In addition, upwards of 17% of cases of SIADH are idiopathic (meaning of unknown origin).
Urine Output and Other SIADH Symptoms
The primary cause of symptoms of SIADH is hyponatremia, a potentially severe electrolyte imbalance that can affect almost every organ system of the body.
Symptoms of SIADH are often subtle or non-existent (asymptomatic) at first but become increasingly obvious and severe as vasopressin secretion persists and sodium concentrations plummet.
SIADH and Urine Output
One of the first signs of SIADH may be decreased urine output accompanied by highly concentrated urine (recognized by a deep yellow color and strong smell). With SIADH, drinking more water doesn’t make the urine any less concentrated because the additional water is simply reabsorbed.
As such, SIADH may be suspected when the amount of water you drink is more than the amount of urine you pee.
As hyponatremia increasingly alters osmosis, causing cells to become overloaded with fluid, an array of symptoms can develop in different parts of the body:
| Body System | Symptoms |
|---|---|
| Neurological | Confusion Delirium Difficulty speaking (dysarthria) Fatigue Headache Irritability Lethargy |
| Neuromuscular | Generalized weakness Involuntary jerks and twitches (myoclonus) Loss of balance and coordination (ataxia) Muscle aches (myalgia) Muscle cramps Tremors Slowed reflexes (hyporeflexia) Uncontrolled flapping movements (asterixis) |
| Gastrointestinal | Loss of appetite (anorexia) Nausea or vomiting |
| Respiratory | Abnormally small breaths (hypopnea) Sudden pauses in breathing while awake (apnea) Sudden pauses in breathing while sleeping (central sleep apnea) |
Complications and Medical Emergencies
SIADH can lead to potentially serious complications if left untreated. If hyponatremia requires hospitalization, the risk of mortality (death) is significant.
According to a 2016 study in BMJ Nephrology involving 64,723 adults, the risk of death among people hospitalized for severe hyponatremia was between 24.5% and 50.3%. People whose sodium levels do not normalize within 24 to 48 hours are at greatest risk.
Complications of SIADH mainly stem from cerebral edema, a condition in which fluids accumulate in the brain. This can cause the bulging (herniation) of the brain and the compression of the brain stem, leading to:
SIADH vs. Diabetes Insipidus
Another condition caused by the abnormal production of vasopressin is diabetes insipidus. Unlike SIADH, diabetes insipidus is caused by the underproduction of vasopressin, leading to increased urination and the risk of dehydration and hypernatremia (high blood sodium).
In cases like this, a synthetic version of vasopressin called DDAVP (desmopressin) can be prescribed to reduce urination and help normalize blood sodium levels.
Confirming SIADH as the Cause of Hyponatremia
SIADH may be recognized by the appearance of acute symptoms. In people with chronic SIADH, the condition may only be recognized when a routine blood test reveals that sodium levels are low.
Diagnosing SIADH can be tricky because hyponatremia has many different causes. To make an accurate diagnosis, your healthcare provider will need to perform a battery of tests, including:
- Antidiuretic hormone (ADH) test: This blood test checks the level of vasopressin in your blood. Normal values range from 0 to 5.9 picograms per milliliter (pg/mL). Anything above 5.9 may be a sign of SIADH.
- Comprehensive metabolic panel (CMP): This panel of blood tests can measure sodium levels in your blood. Levels between 135 and 145 milliequivalents per liter (mEq/L) are considered normal. With hyponatremia, sodium levels will be less than 135 mEq/L.
- Serum osmolality test: This blood test measures the concentration of specific substances in your blood. With SIADH, the test will show sodium concentrations of less than 275 milliosmoles per kilogram of water (mOsm/kg).
- Urinalysis: This test examines the chemical makeup of urine. In addition to noting the color of your urine, SIADH is suspected if sodium levels are high (generally over 40 mEq/L).
It’s worth noting, however, that a high ADH value is not diagnostic of SIADH. This is because some conditions don’t cause the overproduction of vasopressin but instead cause the kidneys to become less sensitive to the effects of vasopressin. This includes nephrogenic SIADH and certain medications.
To confirm the diagnosis, healthcare providers will need to exclude other possible causes of hyponatremia, including:
Thereafter, additional tests may be ordered to pinpoint the underlying cause of SIADH.
Treating SIADH in a Hospital
The treatment of SIADH is twofold: resolving the underlying condition and taking steps to normalize the body’s water-sodium balance.
For mild, asymptomatic SIADH, the latter can be achieved by increasing your dietary sodium intake and restricting your fluid intake to between 1 and 1.5 liters per day until the underlying cause is managed. Drinking water alone will not improve your condition.
If hyponatremia is severe (defined as sodium levels under 120 mEq/L), you will need to be hospitalized so sodium levels can be normalized with intravenous (IV) saline fluids.
In cases like this, the goal of treatment is to raise your sodium levels steadily but not so fast that it causes osmotic demyelination (a condition in which nerves in the brain stem are severely damaged due to the too-rapid shift of fluids from the inside to the outside of cells).
Healthcare providers will generally aim to raise blood sodium levels by no more than 0.5 mEq/L per hour until the optimal balance is achieved.
Other intravenous drugs may also be used to counter the effect of vasopressin. These include:
- Declomycin (demeclocycline): An antibiotic that suppresses the production of vasopressin
- Vaprisol (conivaptan) and Jynarque (tolvaptan): Two drugs classified as aquaretics that block the activation of vasopressin receptors in the kidneys
- Urea: A naturally occurring compound found in urine that may help protect against osmotic demyelination
Prognosis
In people with mild or moderate asymptomatic SIADH, the outlook is generally good with the appropriate treatment.
In people hospitalized with severe SIADH, the odds of recovery are also good if sodium levels are raised at the ideal rate and normalized within 24 to 48 hours.
A 2023 study in the New England Journal of Medicine Evidence examined the records of 3,274 people hospitalized for severe hyponatremia and found that those whose sodium levels were increased by less than 10 mEq/L in 24 hours had a higher risk of death than those whose levels were increased by more than 10 mEq/L in 24 hours.
Summary
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the abnormal retention of fluids due to the excessive production of antidiuretic hormone (ADH), also known as vasopressin. Defects in vasopressin receptors in the kidneys can also cause SIADH.
Common causes of SIADH include cancer, medications, lung diseases, brain injury, and diseases of the central nervous system.
SIADH can be diagnosed with blood and urine tests. Treatment involves resolving the underlying cause and restoring the normal balance of sodium and water in the body. In severe cases, treatment is delivered in a hospital with intravenous saline fluids.
:max_bytes(150000):strip_icc()/Denjay_photo-56f3c0ca5f9b5867a1cc4ccb.jpg)
اكتشاف المزيد من LoveyDoveye
اشترك للحصول على أحدث التدوينات المرسلة إلى بريدك الإلكتروني.