Syndrome of Inappropriate Antidiuretic Hormone Secretion or SIADH is a condition defined by excessive release of antidiuretic hormone (ADH), also known as vasopressin, leading to water retention and hyponatraemia, a state of abnormally low sodium levels in the blood.
The dysregulation in SIADH causes the kidneys to reabsorb excessive amounts of water, reducing the sodium levels in the blood and causing further difficulties. SIADH is associated with a variety of underlying conditions, and its diagnosis requires a careful understanding of both clinical and laboratory results.
In this article, we will delve into the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), examining its causes, symptoms, and management strategies.
SIADH
Syndrome of Inappropriate Antidiuretic Hormone Secretion or SIADH is a medical condition in which excessive amounts of antidiuretic hormone (ADH) are released, leading to water retention and dilution of sodium levels in the body.
It causes hyponatraemia, or low blood sodium, which can result in a variety of symptoms from mild fatigue and confusion to severe neurological disturbances like seizures or coma. SIADH is often caused by underlying conditions such as brain injuries, lung diseases, cancers, or the use of certain medications.
Effective management involves addressing the root cause and carefully correcting the sodium imbalance to avoid complications.
Causes of SIADH
The following are the causes of SIADH:
1. CNS Disorders
CNS diseases, including infections, trauma, and strokes, usually cause SIADH. Improper hormone release can result from disruptions in ADH control in the hypothalamus or pituitary caused by both ischaemic and hemorrhagic strokes. This syndrome may be worsened by hypothalamic-pituitary axis disruption due to inflammation and brain oedema following a stroke.
Trauma, such as brain tumours and head injuries, can also prevent the release of ADH because they cause direct damage to brain tissue or raise intracranial pressure.
Also, central nervous system infections like meningitis and encephalitis can trigger inflammatory responses that disrupt normal ADH production, contributing to water retention and hyponatraemia.
2. Pulmonary Conditions
Pulmonary conditions also play a significant role in the development of SIADH. With the close connection between the respiratory system and the central nervous system, infections such as bacterial or viral pneumonia can cause inflammatory changes in the lungs that affect ADH secretion.
Similar to this, tuberculosis can cause hypoxia and chronic inflammation, which might encourage the release of excessive amounts of ADH, especially when it affects the lungs.
Lung cancer is a general cause of SIADH because malignancies like small-cell lung carcinoma (SCLC) are well-known for generating ectopic ADH. Water and sodium balance may be further complicated by other lung neoplasms that create ADH or cause paraneoplastic disorders.
3. Medications
Certain medications are known to induce SIADH, particularly antidepressants and antipsychotics. Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) can alter neurotransmitter pathways that regulate ADH. At the same time, older antipsychotics like haloperidol may impact dopamine and serotonin pathways, both of which influence ADH secretion. Chemotherapy drugs, too, are associated with SIADH, as they can directly or indirectly alter ADH secretion or sensitivity through cytotoxic effects on various organs, including the kidneys.
4. Malignancies
Malignancies, aside from SCLC, can also contribute to SIADH through ectopic ADH production or alterations in regulatory pathways. Cancers such as prostate and pancreatic cancer may either produce ADH directly or stimulate the body’s production through tumour activity.
Ectopic ADH production is a common mechanism in malignancy-associated SIADH, particularly in cases involving paraneoplastic syndromes, where tumours cause overproduction of hormones like ADH, leading to severe water retention and hyponatraemia.
Symptoms of SIADH
The symptoms of SIADH are primarily related to hyponatraemia, which develops as a result of excessive retention of water and dilution of sodium in the blood. The gravity of symptoms depends on how quickly hyponatraemia develops and the extent of sodium depletion. Symptoms can vary from mild and nonspecific to severe, potentially life-threatening neurological manifestations.
1. Mild Hyponatraemia (Serum Sodium 130-135 mmol/L)
It may go unnoticed or manifest with vague, nonspecific symptoms such as:
Fatigue
Individuals may experience persistent tiredness and low energy levels, which can be mistaken for general fatigue. It may also lead to difficulty concentrating or reduced physical performance.
Nausea and Vomiting
Gastrointestinal symptoms, like vomiting, nausea, and loss of appetite, are expected in the early stages. Occasionally, this is accompanied by mild abdominal discomfort or bloating.
2. Moderate Hyponatraemia (Serum Sodium 120-130 mmol/L)
The following symptoms may become more noticeable:
Confusion and Irritability
Cognitive impairments like focus issues, memory problems, or mental fog become more noticeable. Patients may also exhibit unusual anxiety, mood swings, or irritability.
Muscle Weakness or Cramps
Muscle cramps, weakness, or tremors may develop as a result of electrolyte imbalances. These symptoms can extend to decreased coordination or muscle twitching.
3. Severe Hyponatraemia (Serum Sodium <120 mmol/L)
Potentially life-threatening symptoms such as:
Seizures
As sodium levels drop further, the brain’s ability to function becomes impaired, leading to seizures. These seizures may be brief or prolonged, requiring urgent medical intervention.
Coma
In extreme cases, untreated severe hyponatraemia can lead to coma because of swelling of the brain cells (cerebral oedema). This condition may progress if hyponatraemia is not corrected.
Altered Mental Status
Profound disorientation, confusion, delirium, or even hallucinations can occur. Patients may become unresponsive or exhibit unusual, erratic behaviour.
Respiratory Arrest
In rare, life-threatening cases, respiratory arrest can occur as a result of extreme neurological impairment. It is often preceded by deep lethargy or loss of consciousness.
Management
The management of SIADH primarily focuses on treating the underlying cause and correcting hyponatraemia while avoiding overly rapid correction, which can lead to osmotic demyelination syndrome (ODS), a severe neurological disorder.
1. Fluid Restriction
Fluid restriction is the first line of treatment for the majority of SIADH cases. Restricting daily fluid consumption to 500–1000 mL helps in stopping further plasma sodium dilution. This strategy can be adjusted depending on the severity of hyponatraemia and is frequently successful in mild to moderate cases.
2. Salt Supplementation
Salt tablets may be used to boost sodium intake in moderate cases of hyponatraemia. Fluid restriction should also be used to raise serum sodium levels progressively. Increased sodium intake in the diet is also possible in some circumstances, although careful observation is required to prevent fluid excess.
3. Pharmacotherapy
Demeclocycline and vasopressin receptor antagonists are two medications used in the pharmacotherapy of SIADH (Vaptans). Demeclocycline is a tetracycline antibiotic that is used to treat persistent cases of SIADH, especially when fluid restriction is insufficient to control the disease.
It functions by decreasing the kidneys’ sensitivity to antidiuretic hormone (ADH). However, vasopressin receptor antagonists, such as tolvaptan, prevent the kidneys from being affected by ADH, which makes it easier to release water without losing salt. Since there is a chance of side effects and sudden fluctuations in salt levels, these drugs are usually only used for severe cases of SIADH and require constant monitoring.
4. Hypertonic Saline
An intravenous hypertonic saline solution (3%) is used to quickly raise serum sodium levels in cases of severe or symptomatic hyponatraemia. Careful monitoring is essential to avoid rapid correction, which can result in ODS. Close monitoring of the rate of infusion is critical, and it is often done in an intensive care unit.
Conclusion
In conclusion, the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a complex condition characterised by excessive ADH release, leading to water retention and hyponatraemia. It can manifest from a variety of causes, including neurological disorders, pulmonary diseases, medications, and malignancies. Early recognition and appropriate management are essential, as untreated SIADH can lead to serious complications, including neurological impairment and potentially life-threatening outcomes. With timely intervention and careful monitoring, most patients can recover and maintain proper fluid and electrolyte balance.
