The Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) causes the body to retain too much water due to the uncontrolled release of Antidiuretic Hormone (ADH). This imbalance dilutes the blood, leading to a dangerously low concentration of sodium. SIADH is not a disease itself but a complication of an underlying medical problem. The inappropriate hormonal release stems from a wide range of causes, including various cancers, brain disorders, and reactions to certain medications.
Understanding Antidiuretic Hormone and Water Regulation
The body’s water balance is regulated by Antidiuretic Hormone (ADH), also called vasopressin. This hormone is manufactured in the hypothalamus and stored and released by the posterior pituitary gland. Normally, ADH is released when the body senses dehydration or a high concentration of solutes, such as sodium, in the blood. ADH travels to the kidneys, where it increases water reabsorption back into the bloodstream. This action conserves water and concentrates the urine. SIADH occurs when ADH is released inappropriately, even when the blood is already dilute. The resulting excessive water reabsorption dilutes the blood, creating a state of fluid imbalance.
Cancers and Pulmonary Diseases
Malignancies trigger a significant number of SIADH cases, representing approximately one-quarter of all instances. The most notorious link is with Small Cell Lung Cancer (SCLC), the most common tumor associated with this syndrome. SCLC cells synthesize and secrete ADH directly into the bloodstream, a phenomenon known as a paraneoplastic syndrome. This ectopic production is completely unregulated, continuing regardless of the body’s fluid status. Other cancers, such as head and neck cancers, pancreatic cancer, and lymphomas, also produce the hormone outside the pituitary gland. Furthermore, non-malignant pulmonary diseases, including bacterial or viral pneumonia and tuberculosis, can inappropriately stimulate ADH release. It is theorized that altered pressure receptors or inflammatory signals within the chest cavity may mistakenly signal the brain to release the hormone.
Central Nervous System Disorders
Disorders affecting the central nervous system (CNS) are a major category of SIADH causes. Since the hypothalamus and pituitary gland are located in the brain, any injury or disease in this area can disrupt the hormone’s normal regulatory mechanism. Head trauma, strokes, and bleeding within the brain, such as subarachnoid hemorrhage, can damage the structures responsible for ADH control. Infections like meningitis or encephalitis, which cause inflammation of the brain and its surrounding membranes, are also known triggers. The irritation caused by these conditions can lead to an unregulated, continuous outpouring of ADH from the pituitary gland. Even certain mental illnesses or neurosurgical procedures can result in this inappropriate hormonal secretion.
Drug-Induced SIADH
Many commonly prescribed medications can inadvertently lead to SIADH by interfering with ADH regulation or mimicking its action on the kidneys. Drug-induced SIADH is a frequent cause, especially in older adults taking multiple medications. A prominent class of implicated drugs includes certain antidepressants, particularly Selective Serotonin Reuptake Inhibitors (SSRIs), which stimulate ADH release. Anticonvulsant medications, such as carbamazepine, increase the kidney’s sensitivity to ADH effects. Certain chemotherapy agents, like cyclophosphamide and vincristine, are also known to stimulate ADH release or potentiate its action. Other pharmacological agents, including some opiates and antipsychotic drugs, can contribute to the problem. A careful review of a patient’s medication list is necessary for diagnosing the cause of SIADH.
Consequences: The Danger of Hyponatremia
Regardless of the underlying cause, the physiological result of SIADH is dilutional hyponatremia, a low sodium concentration in the blood. The excessive water retention dilutes the body’s sodium, which determines the fluid balance outside of cells. Mild hyponatremia may produce subtle symptoms like nausea, loss of appetite, or general malaise. As sodium levels drop, symptoms become more serious, reflecting the effect on the brain. Water shifts into brain cells to balance the low concentration of solutes, causing the brain to swell. Moderate to severe hyponatremia can lead to confusion, headache, muscle weakness, and balance problems. In the most severe cases, very low sodium levels can precipitate seizures, coma, and potentially permanent brain damage or death.