Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a condition where the body produces an excess of antidiuretic hormone (ADH), leading to an imbalance in water and sodium levels. This overproduction causes the body to retain too much water, which in turn dilutes the sodium in the blood.
Understanding Antidiuretic Hormone
Antidiuretic hormone (ADH), also known as vasopressin, is a hormone produced in the hypothalamus and released by the posterior pituitary gland. Its primary function is to help the kidneys regulate the body’s water balance. ADH signals the kidneys to reabsorb water from urine back into the bloodstream, thereby concentrating urine and conserving body fluid.
Under normal circumstances, ADH release is regulated by the body’s hydration status and blood concentration. If the blood becomes too concentrated, ADH is released to prompt water reabsorption, diluting the blood and restoring balance. In SIADH, however, ADH is released inappropriately, meaning it is secreted even when the body does not need to conserve water.
Primary Medical Causes of SIADH
Malignancies, particularly small cell lung cancer (SCLC), are common causes of SIADH. SCLC cells can directly produce and secrete ADH, a phenomenon known as ectopic production. This inappropriate ADH release from cancer cells is not regulated by the body’s normal feedback mechanisms.
Other cancers, though less frequently, can also lead to SIADH, including those of the pancreas, prostate, and lymphomas. In these instances, the cancerous cells may also produce ADH ectopically, or they might trigger the release of ADH through other indirect mechanisms. The presence of SIADH in cancer patients can sometimes indicate a more advanced stage of the disease.
Pulmonary conditions, especially infections like pneumonia and tuberculosis, can also trigger SIADH. While the exact mechanisms are not fully understood, inflammation or changes in lung mechanics associated with these conditions may stimulate ADH release. Other lung diseases, such as asthma and cystic fibrosis, have also been infrequently linked to SIADH.
Central Nervous System (CNS) disorders represent another category of SIADH causes. Conditions affecting the brain or spinal cord, such as stroke, hemorrhage, meningitis, encephalitis, brain tumors, and head trauma, can disrupt the normal regulation of ADH. Damage or irritation to the hypothalamus or pituitary gland, where ADH is produced and stored, can lead to its uncontrolled secretion.
For instance, traumatic brain injury can result in SIADH due to direct damage to the hypothalamic-neurohypophyseal system. Similarly, subarachnoid hemorrhage and increased intracranial pressure can interfere with ADH regulation. These neurological insults can cause the pituitary gland to release ADH without proper physiological cues.
Other Factors That Can Trigger SIADH
Various medications are known to induce SIADH by either stimulating ADH release or enhancing its effects on the kidneys. Common culprits include certain antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), which can alter brain chemistry leading to increased ADH secretion. Antiepileptic drugs like carbamazepine are also frequently implicated.
Chemotherapy agents, such as vincristine and cyclophosphamide, can also cause SIADH, sometimes through direct toxic effects on the neurohypophysis. Some pain medications have also been associated with this condition. The mechanism often involves either direct stimulation of ADH release or increased sensitivity of the kidneys to the hormone.
Acute conditions and physiological stressors can also temporarily induce SIADH. Severe pain, intense nausea and vomiting, and major surgical procedures are examples of such stressors. The body’s response to these events can include a temporary increase in ADH release, leading to water retention.
In some instances, no clear underlying cause for SIADH can be identified, and the condition is then termed idiopathic SIADH. This form is observed in a notable percentage of cases, ranging from approximately 17% to 60%, and appears to be more common in older adults. The reason for the inappropriate ADH secretion remains unknown in these individuals.