From the Guidelines
Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion is diagnosed based on euvolemic hypoosmolar hyponatremia, characterized by low serum osmolality and inappropriately high urine osmolality, and managed with free water restriction, hypertonic saline, and vasopressin 2 receptor antagonists.
Diagnosis of SIADH
- Hyponatremia (serum sodium < 134 mEq/L) is a key feature of SIADH, with symptoms determined by the degree of hyponatremia and the acuity of hypoosmolality 1.
- Hypoosmolality (plasma osmolality < 275 mosm/kg) and inappropriately high urine osmolality (> 500 mosm/kg) are also essential for diagnosis 1.
- Inappropriately high urinary sodium concentration (> 20 mEq/L) and absence of hypothyroidism or adrenal insufficiency or volume depletion are additional diagnostic criteria 1.
Management of SIADH
- Free water restriction (< 1 L/d) is a first-line treatment for asymptomatic mild SIADH and a recommended adjunct to other therapy for severe cases 1.
- Hypertonic 3% saline IV is given in life-threatening or acute symptomatic and severe (< 120 mEq/L) hyponatremia 1.
- Vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) may also be used to correct hyponatremia, as well as demeclocycline and lithium 1.
Clinical Considerations
- Small cell lung cancer (SCLC) is a common cause of SIADH, with approximately 10% to 45% of SCLC cases producing arginine vasopressin (ie, antidiuretic hormone [ADH]) 1.
- Other medications, such as chemotherapeutic agents, opioids, non-steroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and antidepressants, can also cause SIADH 1.
- Early detection and appropriate management of SIADH can prevent severe hyponatremia, which can lead to seizures, coma, and death 1.
From the Research
Diagnosis of SIADH
- The diagnosis of SIADH should be considered if the five cardinal criteria are fulfilled: hypotonic hyponatraemia, natriuresis, urine osmolality in excess of plasma osmolality, absence of oedema and volume depletion, and normal renal and adrenal function 2
- Diagnosis involves a precise evaluation of volemia and the elimination of differential diagnoses 3
- The clinical features are principally neuro-muscular and gastro-intestinal, the severity of which is related to both the absolute serum sodium concentration and its rate of fall, particularly if greater than 0.5 mmol/1/h 2
Causes of SIADH
- The major groups of causes of SIADH are: (i) neoplasia, (ii) neurological diseases, (iii) lung diseases, and (iv) a wide variety of drugs 2
- Inappropriate infusion of hypotonic fluids in the post-operative state remains a common cause 2
- The etiologies are classified into four main groups: tumors, drugs, diseases of the central nervous system, and lung diseases 3
Management of SIADH
- For symptomatic patients with chronic SIADH, the mainstay of therapy remains fluid restriction 2, 4
- Immediate treatment of the symptomatic patient with SIADH includes intravenous furosemide and 3% sodium chloride injection to produce a negative free-water balance 4
- Hypertonic saline remains the gold standard in the initial treatment of symptomatic SIADH with severe neurological deficits 5
- New antagonists to the antidiuretic action of AVP, such as vaptans, offer a new therapeutic approach 2, 5
- Fluid restriction and demeclocyclin have been the most widely used treatments for chronic hyponatremia in SIADH, but vaptans have been shown to be efficacious both during short-term and long-term administration 5
Treatment Considerations
- Correction of hyponatremia needs to be slow (<10-12 mmol/l within the first 24 h, and <18 mmol/l within the first 48 h, respectively) to avoid osmotic myelinolysis 5
- Only the etiologic treatment leads to the disappearance of SIADH 3
- Treatment of SIADH consists of elimination of underlying causes and restriction of fluid intake; if these measures are unsuccessful or poorly tolerated, long-term drug therapy may be indicated 4