SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion) is a disorder affecting the body’s balance of water and salt. It involves the excessive release of Antidiuretic Hormone (ADH), which regulates water retention. When too much ADH is present, the body retains excessive water instead of eliminating it through urine. This excess fluid dilutes the blood, causing a lower-than-normal concentration of sodium. The resulting state, known as dilutional hyponatremia, is the defining feature of SIADH.
How the Body Regulates Water and Sodium
The entire process of water balance centers on Antidiuretic Hormone (ADH), also called vasopressin. This hormone is normally produced in the hypothalamus and released from the pituitary gland. The primary trigger for release is an increase in the blood’s osmolality, or concentration, which signals dehydration.
Once released, ADH travels to the kidneys, where it increases the permeability of the collecting ducts. This action allows the kidneys to reabsorb more water back into the bloodstream instead of letting it pass out as urine. This mechanism conserves body water, concentrating the urine and restoring the blood’s normal balance.
In SIADH, the term “inappropriate” means that ADH is released even when the blood’s osmolality is low or the body’s water volume is adequate. This unsuppressed hormone continues to signal the kidneys to conserve water, creating chronic water retention.
Because the body retains water without retaining a proportional amount of sodium, the plasma concentration falls below the normal range (135 to 145 milliequivalents per liter). This hyponatremia is caused by water excess. The excessive water retention also causes the urine to be inappropriately concentrated, as the kidneys continuously save water despite the diluted state of the blood.
Factors That Cause Inappropriate ADH Release
The triggers for the inappropriate release of ADH are varied and often involve underlying systemic illnesses.
Malignancies
Certain malignancies are well-documented causes, with small cell lung carcinoma being the most frequent tumor associated with SIADH. These cancerous cells sometimes produce and secrete ADH themselves, a phenomenon known as ectopic hormone production.
Central Nervous System Disorders
Disorders affecting the central nervous system can also stimulate the pituitary gland to release ADH. Conditions such as stroke, cerebral hemorrhage, brain infections like meningitis, or head trauma can disrupt the normal regulatory signals.
Pulmonary Conditions
Various pulmonary conditions, including severe pneumonia, tuberculosis, and respiratory failure, are known to cause SIADH. The exact physiological connection between these conditions and ADH release is not fully understood.
Medications
A number of prescription medications can interfere with the normal ADH regulation pathway. These include certain antidepressants (especially SSRIs), specific chemotherapy agents, seizure medications, and antipsychotic drugs. Reviewing a patient’s medication list is an important diagnostic step.
Physical Signs of Low Sodium Levels
The symptoms of SIADH relate directly to the severity and speed of the sodium concentration drop. Mild hyponatremia (130 to 135 mEq/L) may cause no noticeable symptoms. As the level drops below 130 mEq/L, patients often experience non-specific complaints like headache, nausea, or malaise.
When the sodium level falls below 125 mEq/L, symptoms become more pronounced and affect the neurological system. Patients may exhibit lethargy, confusion, or difficulty with balance and gait. The brain is sensitive to these changes because low sodium causes water to shift into the brain cells, leading to cellular swelling.
Severe hyponatremia, defined as a serum sodium level below 120 mEq/L, represents a medical emergency. This level of dilution can cause significant cerebral edema, leading to severe neurological issues such as seizures, delirium, and coma. Symptoms are much greater when the sodium level drops rapidly (less than 48 hours) compared to a gradual decline.
Identifying and Treating SIADH
Diagnosis
Diagnosing SIADH requires specific laboratory findings to confirm dilutional hyponatremia and exclude other causes of low sodium. Blood tests show low plasma osmolality and a serum sodium concentration below 135 mEq/L. These results must be accompanied by urine tests showing an inappropriately high urine osmolality (typically over 100 mOsm/kg) and a high urine sodium concentration.
Initial Management
Initial management focuses on treating the underlying cause, such as a medication, infection, or malignancy. Fluid restriction is the first-line therapy, limiting total fluid consumption to less than the patient’s daily urine output (often 800 to 1200 milliliters per day). This strategy aims to create a negative water balance, allowing the kidneys to excrete the excess water.
Severe Hyponatremia Treatment
For patients experiencing severe symptoms like seizures or altered mental status, urgent and controlled correction of the sodium level is necessary. This involves the intravenous administration of hypertonic saline, a concentrated salt solution, to quickly draw water out of the swollen brain cells. The correction must be performed slowly and carefully to prevent osmotic demyelination syndrome (ODS).
Chronic and Resistant Cases
In chronic or resistant cases, medications can be used to manage the condition. A class of drugs called vasopressin receptor antagonists (vaptans) blocks the action of ADH on the kidney, promoting the excretion of free water without losing sodium. Other therapies, such as oral urea, increase the solute load in the kidney, encouraging water to be pulled out of the body through osmotic diuresis.