The syndrome of inappropriate antidiuretic hormone (SIADH) is defined by inappropriate secretion of antidiuretic hormone resulting in hyponatremia and hypoosmolality in the setting of normal or increased plasma volume, leading to impaired water excretion. SIADH is caused either by inappropriate secretion of antidiuretic hormone (ADH) from the hypothalamus or from an ectopic source. SIADH may arise from postoperative stress, pain, or nausea. It also commonly manifests as a paraneoplastic syndrome.

Causes of SIADH can be divided into the following categories (more than one cause is often present, and sometimes no cause is identified):

• Nervous system disorders – Head trauma, meningitis, encephalitis, subdural hematoma, subarachnoid hemorrhage, Guillain-Barre syndrome, multiple sclerosis, amyotrophic lateral sclerosis, ventriculoperitoneal shunt occlusion, Shy-Drager syndrome, and cerebrovascular accident.
• Neoplasia – Small cell lung cancer, non-small cell lung cancer, mesothelioma, bronchial adenoma, primary brain tumors, thymoma, Ewing sarcoma, non-Hodgkin lymphoma, stomach cancer, neuroendocrine carcinomas, duodenal cancer, pancreatic cancer, bladder cancer, and uterine cancer.
• Pulmonary diseases – Chronic obstructive pulmonary disease, cystic fibrosis, pneumonia, asthma, pneumothorax, acute respiratory failure requiring mechanical ventilation, pulmonary aspergillosis, pulmonary fibrosis, tuberculosis, and sarcoidosis.
• Drug-induced SIADH – Antidepressants, especially selective serotonin reuptake inhibitors and monoamine oxidase inhibitors; chemotherapeutic agents including cyclophosphamide, ifosfamide, vincristine, vinblastine, cisplatin, and melphalan; ciprofloxacin; griseofulvin; carbamazepine; chlorpropamide; high-dose oxytocin; and vasopressin or desmopressin.

Hyponatremia is the most common electrolyte derangement. Elderly patients, adults with cirrhosis or heart failure, patients with cancer, and children with pulmonary or gastrointestinal infections are at highest risk for developing SIADH.

Presenting symptoms relate to the rapidity of development of hyponatremia. Patients with slowly progressive hyponatremia are often asymptomatic, while those with rapid development of hyponatremia may present with headache, confusion, anorexia, malaise, or even seizures and coma. Physical examination often reveals a normotensive and euvolemic patient.