SIADH

SIADH is characterized by excessive and inappropriate secretion of Antidiuretic Hormone (ADH), leading to an inability of the body's negative feedback mechanism to regulate ADH production. This excessive ADH causes water retention within the body.

Modifiable risk factors include certain medications like SSRIs (especially in patients 65 and older), TCAs (which stimulate ADH release), Carbamazepine (increases ADH release and kidney sensitivity to ADH), Cyclophosphamide and Vinblastine (antineoplastic agents, particularly with excessive fluid administration), Desmopressin (synthetic ADH), excessive hypotonic solution intake (e.g., D5W), poor fluid regulation, substance abuse (ecstasy stimulates ADH release and induces polydipsia), and uncontrolled pain and stress (stimulate non-osmotic ADH release).

Non-modifiable risk factors include advanced age (elderly patients are more susceptible), certain cancers like small cell lung carcinoma (the most common cancer associated with SIADH, as the tumor mimics ADH release), pancreatic cancer (emerging risk), prostate cancer (rare but documented instances), and brain cancer (causes disruption in the hypothalamus and pituitary gland). Other factors include CNS disorders like stroke and brain injury (trigger excessive ADH release), infections such as meningitis and encephalitis (cause inflammation leading to SIADH), pulmonary disorders like TB and pneumonia (cause ectopic ADH release and stress-induced ADH stimulation), and post-neurosurgery (disrupts normal hormone regulation).

Exposure to these risk factors triggers inappropriate ADH secretion. Increased ADH makes renal collecting tubules more sensitive, leading to increased water reabsorption. This results in increased intravascular volume without sodium retention, causing a rise in blood pressure and a bounding pulse. The kidneys continue to excrete sodium, leading to increased urine sodium and urine concentration, but decreased urine output. The excessive fluid dilutes serum sodium, leading to dilutional hyponatremia and decreased serum osmolality. This causes water to shift from the intravascular space into brain cells, resulting in cerebral edema and increased intracranial pressure (ICP).

Neurologic symptoms vary by severity: mild symptoms include anorexia, nausea, fatigue, and mild confusion; moderate symptoms include muscle cramps, weakness, vomiting, lethargy, and disorientation; severe symptoms can involve seizures, decreased level of consciousness, coma, and respiratory arrest, potentially leading to death due to increased ICP. Complications include cerebral edema, seizure, coma, respiratory failure, hyponatremic encephalopathy, and osmotic demyelination syndrome (caused by rapid correction of fluid imbalances).