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Syndrome of Inappropriate Anti-Diuretic Hormone

SIADH- syndrome of inappropriate anti-diuretic hormone
Occurs when ADH is secreted in excess.
In the distal nephron, we show that excessive ADH secretion results in unregulated aquaporin creation and insertion in the nephron, which leads to increased water reabsorption.
    • Thus, the urine produced is highly concentrated (low volume, high osmolality).
Signs and Symptoms: Patients present with hyponatremia and low serum osmolality.
We might expect that the patients would be hypervolemic, but this is often only a transient state due to natriuretic mechanisms that respond to expanded body water volume.
Some patients are asymptomatic, but if serum sodium levels fall too low and/or too rapidly, patients can experience nausea/vomiting, obtundation (a state of reduced alertness due to diminished consciousness), headaches, seizures, respiratory arrest, even coma and death.
Neurologic symptoms occur when excessive water reabsorption causes brain swelling and neuron dysfunction; this typically occurs at serum sodium levels below 120 mEq/L.
Causes: SIADH can be caused by CNS disorders (including stroke, infection, hemorrhage), tumors that secrete ectopic ADH (particularly in Small Cell Lung Cancer), drugs (including some analgesics, antiseizures meds, SSRIs, and antipsychotics), surgery, infections (particularly lung infections like TB and pneumonia, or HIV), and, that there are some inherited disorders that cause SIADH. For more details, please see the links in our notes.
Treatment for SIADH includes ADH antagonists, treatment of underlying causes, and fluid restriction.
More complete list of causes:
    • Ectopic tumor secretion
Carcinoma of bronchi, duodenum, pancreas, ureters, bladder, uterus. Thymoma Mesothelioma Lymphoma/leukemia
    • Drugs
Tricyclic and SSRI antidepressants MOAIs Chlorpropamide Carbamazepine Clofibrate Ecstasy Vinca alkaloids Cisplatin Cyclophosphamide Desmopressin Oxytocin
    • Neural pathway disruption
CNS disorders (infection, trauma/surgery, hemorrhage, inflammatory and degenerative diseases) Pulmonary disorders (TB, pneumonia, fungal infections, empyema, and positive pressure ventilation)
    • Nephrogenic SIADH: mutation that causes chronic activation of V2 receptor
    • Other (AIDS, strenuous physical activity, such as marathon running, psychosis)