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Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)


Definition

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is caused by excessive or inappropriate secretion or action of antidiuretic hormone (ADH), resulting in:

  • Dilutional hyponatremia without clinically apparent hypervolemia (also known as euvolemic)

  • Reduced plasma osmolality

  • Impaired water excretion with decreased volumes of urine that is inappropriately concentrated for the prevailing plasma osmolality and volume status.

Schwartz first described SIADH in 1957 (also known as Schwartz–Bartter syndrome). SIADH is uncommon in the general population and is mainly seen in hospitalized patients. Both genders are equally affected. Risk factors for SIADH are neoplasms, central nervous system (CNS) disorders, pulmonary disease, and some medications; elderly patients are also at a high risk for SIADH.

Etiology

ADH, or arginine vasopressin (AVP), is secreted from the posterior pituitary in response to hypovolemia or hyperosmolality. Physiological action of ADH is to cause water reabsorption from renal tubules, causing concentration of urine. In SIADH, secretion of ADH is unregulated and is secreted despite serum hypotonicity. This leads to retention of water by the kidneys and hypotonic euvolemic hyponatremia. SIADH is the most common cause of euvolemic hyponatremia.

Mechanisms of increased production of ADH include:

  • 1.

    Increased production of ADH from posterior pituitary

  • 2.

    Ectopic production of ADH from primary or metastatic tumor

  • 3.

    Exogenous administration of ADH or its analog (e.g., desmopressin, high-dose oxytocin, chlorpropamide, carbamazepine, vincristine, etc.)

Various conditions that may produce SIADH are given in Table 1 . The most common cause of hyponatremia after acute nontraumatic aneurysmal subarachnoid hemorrhage is SIADH followed by glucocorticoid insufficiency and cerebral salt wasting syndrome (CSWS).

Table 1
Etiologies of SIADH
  • 1.

    Neoplasm: Various tumors that can secrete ADH ectopically such as:

    • a.

      Carcinomas

      • -

        Small-cell carcinoma of the lung (most common neoplastic cause of SIADH)

      • -

        Duodenum, pancreas, ovary, prostrate, urinary bladder, ureter

      • -

        Head and neck

    • b.

      Other neoplasms

      • -

        Thymoma, mesothelioma, bronchial adenoma, carcinoid, gangliocytoma, lymphomas, Ewing’s sarcoma

  • 2.

    Neurological disorders:

    • a.

      CNS disorders

      • -

        Head trauma

      • -

        Postcraniotomy following pituitary surgery, craniopharyngiomas, hypothalamic tumors

      • -

        Brain tumors

      • -

        Stroke (cerebrovascular occlusion, intracranial hemorrhage)

      • -

        Cavernous sinus thrombosis

      • -

        Infection: Meningitis (bacterial, tubercular, or viral), encephalitis, brain abscess, AIDS

      • -

        Hydrocephalus

      • -

        Neurosarcoidosis, multiple sclerosis, amyotrophic lateral sclerosis

      • -

        Psychosis, delirium tremens

      • -

        Congenital malformations: Agenesis of corpus callosum, cleft lip/palate with or without recognized CNS abnormality

    • b.

      Peripheral nervous system disease

      • -

        Guillain–Barré syndrome

      • -

        Peripheral neuropathy

  • 3.

    Pulmonary/Thoracic disorder:

    • a.

      Infection: Pneumonia (bacterial or viral), lung abscess, tuberculosis, AIDS-related lung infections

    • b.

      Cavitation (tuberculosis, aspergillosis)

    • c.

      Chronic obstructive pulmonary disease, asthma

    • d.

      Pneumothorax, pulmonary embolism, atelectasis

    • e.

      Positive-pressure ventilation

  • 4.

    Drugs

    • a.

      Vasopressin or desmopressin, chlorpropamide, high-dose oxytocin, vincristine, carbamazepine, nicotine, phenothiazines, cyclophosphamide, tricyclic antidepressants, monoamine oxidase inhibitors, serotonin reuptake inhibitors, opioids, NSAIDs, theophylline, bromocriptine, clofibrate

  • 5.

    Miscellaneous

    • a.

      Anemia, stress, severe pain, nausea, endurance exercise combined with solute-free water intake

    • b.

      Major surgery, general anesthesia, postoperative pain

    • c.

      Acute intermittent porphyria

    • d.

      Idiopathic

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