What is Syndrome of Inappropriate Antidiuretic Hormone Secretion?
The Syndrome of Inappropriate Antidiuretic Hormone Release (SIADH) is a condition where there is uncontrolled release of the antidiuretic hormone, also known as ADH, from either the brain’s pituitary gland or other sources outside the pituitary gland. This hormone mainly acts on receptors called vasopressin receptors in our body. SIADH was first identified in two lung cancer patients by doctors named William Schwartz and Frederic Bartter in 1967. They also created a set of diagnostic criteria for SIADH, which are still being used today.
SIADH is marked by an inability of your body to properly get rid of water, leading to a condition called hyponatremia. Hyponatremia happens when the sodium levels in your body are unusually low because of too much water. Along with hyponatremia, this could also result in hypervolemia or euvolemia, meaning you have an excessive or normal, respectively, amount of circulating fluid (like blood) in your body.
What Causes Syndrome of Inappropriate Antidiuretic Hormone Secretion?
Usually, SIADH (Syndrome of Inappropriate Anti-diuretic Hormone Secretion) is triggered by another disease somewhere else in the body. However, there’s also a hereditary type of SIADH, which happens due to changes in certain genes that affect the functioning of vasopressin 2, a protein present in your kidneys.
Let’s discuss a few conditions that commonly lead to SIADH:
1. Problems affecting the brain: Any mental or physical issue affecting the brain can enhance the release of ADH (Anti-diuretic Hormone) from the pituitary gland. These issues could include stroke, bleeding in the brain, infection, injuries, mental illness, and psychosis.
2. Certain types of cancer: Small cell lung cancer is the most common type of cancer that leads to extra ADH production. Less commonly, extrapulmonary small cell carcinomas, head and neck cancers, and a type of cancer known as an olfactory neuroblastoma can also cause excess ADH release.
3. Medications: Some drugs can cause SIADH by either increasing the release or effect of ADH. These drugs include carbamazepine, oxcarbazepine, chlorpropamide, cyclophosphamide, and selective serotonin reuptake inhibitors (SSRIs).
4. Surgery: Surgeries can sometimes cause an increase in the secretion of ADH — this is often due to the body’s response to pain.
5. Lung diseases: Certain lung diseases like pneumonia can cause SIADH through unknown mechanisms. Other lung conditions like asthma, atelectasis, acute respiratory failure, and pneumothorax have been occasionally linked to SIADH.
6. Hormone deficiency and administration: Conditions caused by a lack of hormones, like hypopituitarism and hypothyroidism, can sometimes look like SIADH and cause a similar picture. On the other hand, administering certain hormones can induce SIADH as well.
7. HIV infection: Patients with HIV often have low levels of sodium in their blood, which might be due to SIADH. This could also be caused by decreased blood volume due to adrenal insufficiency or gastrointestinal losses.
8. Hereditary SIADH: In some people, a certain change in the genes responsible for the creation of vasopressin 2 receptors in the kidneys can cause a form of SIADH. These genetic changes cause excessive water absorption leading to lower sodium levels in the blood, a situation that is resistant to treatment with vasopressin receptor antagonists.
Risk Factors and Frequency for Syndrome of Inappropriate Antidiuretic Hormone Secretion
The occurrence of a condition called SIADH tends to go up as people age. However, recently, more instances of the condition have been reported in children. Children and elderly people, especially those in the hospital due to respiratory and brain infections such as pneumonia or meningitis, commonly show low sodium levels, which is one of the signs of SIADH.
This condition is also frequently found in people who are in hospital after surgery. This can be caused by being given fluids that have a low salt content, certain medications, and the way your body reacts to stress.
Signs and Symptoms of Syndrome of Inappropriate Antidiuretic Hormone Secretion
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) refers to a condition where the body produces too much antidiuretic hormone, resulting in water retention and low sodium levels in the blood. This often leads to swelling of cells, including those in the brain. The signs and symptoms depend on how quickly and how severe the low sodium levels develop, and how much swelling occurs in the brain.
When sodium levels fall abruptly and significantly, patients may experience symptoms like nausea and a sense of discomfort. Vomiting can be a serious indicator when sodium levels drop suddenly. If sodium levels continue to fall further, symptoms can progress to include severe headaches, fatigue, slowness, and even seizures. In severe cases, this could lead to coma or difficulties in breathing. If sodium drops below a certain threshold, irreversible brain damage or even death could occur, especially in women before menopause.
However, if the drop in sodium progresses slowly, patients might show fewer symptoms even with significantly low sodium levels. Common signs of chronic or long-term low sodium may include nausea, vomiting, walking difficulties, memory issues, cognitive issues, tiredness, confusion, and muscle cramping. These signs are often subtle and can be missed during medical evaluation. Approximately one out of three patients with chronic low sodium, who have a specifically low sodium concentration, experience nausea and vomiting. In elderly patients, long-term low sodium can impact their balance and result in falls, fractures, or walking difficulties.
- Sudden, severe low sodium: nausea, sense of discomfort, vomiting, headache, fatigue, slowness, and potential seizures.
- Chronic, mild low sodium: nausea, vomiting, walking difficulties, memory issues, cognitive problems, tiredness, confusion, and muscle cramping.
- Particularly in elderly patients: balance issues, falls, fractures, walking problems.
Doctors assessing patients suspected of having SIADH must inquire about any head injuries, chronic pain, smoking habits, weight changes, lung-related symptoms, or substance abuse in addition to evaluating the above-mentioned symptoms. Understanding the origin of the excess fluid in the body and for how long the condition has been present is also critical. Physical checkups typically involve checking the patient’s overall fluid status, skin elasticity, and blood pressure. Normal skin elasticity, blood pressure, and lack of signs like jugular vein swelling typically indicate a normal body fluid status. Thorough neurological and chest examinations are necessary to assess the patient’s condition.
Testing for Syndrome of Inappropriate Antidiuretic Hormone Secretion
Detecting the Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) is not as straightforward as with other conditions because no single test can confirm it. Typically, patients suffering from SIADH have a lower than normal sodium level in their blood but with no obvious signs of dehydration. A set of conditions known as the Schwartz and Bartter Clinical Criteria, which have been in use since 1967, are used to identify this syndrome.
According to the Schwartz and Bartter Clinical Criteria, the conditions for SIADH are as follows:
- A blood sodium level less than 135 mEq/L
- A blood osmolality (measure of compound concentration in your blood) less than 275 mOsm/kg
- A urine sodium level higher than 40 mEq/L. This is due to too much water being absorbed back into your body by the kidneys.
- A urine osmolality higher than 100 mOsm/kg
- No evidence of dehydration – normal skin turgor (elasticity) and normal blood pressure
- No other causes of low sodium levels – This could include various diseases like abnormally weak adrenal or thyroid glands, heart failure, conditions affecting pituitary gland (which controls many different body functions), kidney diseases, liver disease, or drugs that impair the kidney’s ability to get rid of water.
- Improvement of low sodium levels by restricting fluid intake
Tests to check blood sugar levels and kidney function are usually done to rule out other conditions, such as high blood sugar or uremia (excess of waste products in the blood), that can also lead to low blood sodium levels.
Tests specific for diagnosing SIADH include:
- Testing blood and urine osmolality and sodium levels
- Testing kidney function
- Testing random blood sugar
- Examining thyroid hormone levels
- Testing the level of cortisol (a hormone produced by adrenal glands)
- Testing blood levels of potassium, bicarbonate, and chloride
- Fasting lipid profile
- Liver function tests
It’s essential to rule out conditions like underactive thyroid (hypothyroidism) and insufficient adrenal glands (adrenal insufficiency) before diagnosing SIADH. If the initial signs and tests point towards SIADH, other tests may be needed to determine the potential root cause based on the patient’s medical history. For instance, if the patient has a history of smoking, weight loss, or lung-related symptoms, additional tests like chest X-ray or CT scan may be required to screen for a type of lung cancer known as SCLC.
Treatment Options for Syndrome of Inappropriate Antidiuretic Hormone Secretion
Patients with the condition SIADH, which causes the body to retain too much water and lose too much of certain substances, are typically treated by carefully correcting and maintaining the right levels of sodium and addressing any underlying issues such as thyroid problems or certain types of infections. The target is to get sodium levels above 130 mEq/L, which is a measure doctors use to check the amount of sodium in the blood.
The right course of treatment depends on how severe the patient’s symptoms are. Even a small, rapid drop in sodium levels can cause serious symptoms like confusion, hallucinations, and seizures. On the other hand, long-standing but significant low sodium levels might have mild or no evident symptoms. For patients with mild to moderate symptoms, the main course of treatment usually includes limiting how much water they drink to help manage the imbalance – ideally, they should drink less than 800 mL per day. If this restriction does not improve the sodium levels, treatments may include the administration of sodium chloride, which can be given through the mouth as a tablet or through a vein as a saline solution. Loop diuretics, a type of water pill that helps your body get rid of extra water and salt, might also be included.
In order to get the sodium levels back to normal, medical professionals will also take note of the concentration of molecules in the urine, as it’s typically twice that of the blood in such patients. The fluid used to correct the sodium levels needs to have a concentration that’s higher than that of urine. Isotonic saline, a common solution given in a vein, might not work, or could even make the low sodium levels worse. In these cases, a solution with a higher concentration of electrolytes, like three percent hypertonic saline, might be used. But it’s important to keep in mind that changing sodium levels too fast can cause serious complications, so doctors make sure it does not increase by more than 8 mEq/L in 24 hours or 0.5-1 mEq/L per hour.
For those with severe symptoms like seizures, confusion, or hallucinations, urgent treatment with hypertonic saline infusion is needed rather than just limiting water intake. This involves giving the patient a certain amount of the solution over a few hours and regularly checking sodium levels to avoid any rapid changes. If the patient’s mental condition does not improve, more doses of hypertonic saline can be given until the patient starts to get better.
There are also specific drugs that can be used to treat severe, persistent SIADH. These block certain receptors in the body to prevent retention of excess water and help correct low sodium levels. One of these drugs should be avoided in patients with liver disease due to possible harmful effects. When these drugs work well, they can help restore normal sodium levels and the patient’s normal mental condition while they’re in the hospital. Other treatments are only used if all other methods don’t work because they can potentially be harmful to the kidneys and have other side effects.
What else can Syndrome of Inappropriate Antidiuretic Hormone Secretion be?
If we are diagnosing SIADH, we also need to think about all the possible causes for low sodium levels in the blood, otherwise known as hyponatremia.
The levels of concentration in the blood and urine can help determine the cause. This concentration is measured in osmolality. If a patient’s blood osmolality is reduced and their urine osmolality is greater than 100mOsm/kg, we then need to assess their body’s water content, and judge the potential cause based on whether they have:
- A normal body water content (Euvolemia) – The cause could be SIADH
- Too much body water (Hypervolemia) – The cause could be cardiac failure or cirrhosis
- Too little body water (Hypovolemia) – The cause could be vomiting or diarrhea
What to expect with Syndrome of Inappropriate Antidiuretic Hormone Secretion
The outlook for patients with SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion), a condition that makes your body produce too much antidiuretic hormone, depends on what’s causing the condition, the impact of severe low sodium levels in the blood (hyponatremia), and the potential consequences of fixing it too quickly. Typically, if SIADH is caused by medication, a patient’s condition often improves quickly once they stop taking the drug.
Possible Complications When Diagnosed with Syndrome of Inappropriate Antidiuretic Hormone Secretion
The complications of SIADH, or Syndrome of Inappropriate Antidiuretic Hormone, depend on how much the sodium levels in the blood decrease. Possible complications may include:
- Headaches
- Memory problems
- Depression
- Tremors
- Muscle cramps
If sodium levels drop extremely low, more serious complications may occur, such as:
- Respiratory failure
- Seizures
- Hallucinations
- Coma
- Death
Preventing Syndrome of Inappropriate Antidiuretic Hormone Secretion
It’s crucial for the patient to strictly monitor and control their fluid intake to avoid any additional buildup. This means that they also need to be familiar with the warning signs and symptoms of two conditions – hypo and hypernatremia – which involve imbalances in sodium levels in the body. If they notice any of these signs, they should immediately get in touch with their healthcare provider. It’s also crucial to follow the prescribed treatment for the root cause of their condition.
