Chapter 24-19: Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

TEXTBOOK PRESENTATION

Patients are often elderly, with a chief complaint of falls, weakness, or confusion. Alternatively, mild hyponatremia may be discovered incidentally on serum chemistries.

DISEASE HIGHLIGHTS

1. Most common cause of hyponatremia

2. Secondary to inappropriate ADH release despite hypotonicity and euvolemia.

3. Despite water retention, patients appear clinically euvolemic. Subtle increase in volume leads to urinary sodium loss.

4. Etiologies: A large variety of diseases may cause SIADH including

   1. Neurologic disease, 9–26%: eg, subarachnoid hemorrhage, stroke, meningitis, tumors, or trauma

   2. Intrathoracic disease, 11–19%: eg, pneumonia, tuberculosis, acute respiratory failure

   3. Cancer, 18–25%: Ectopic production of ADH by small cell carcinoma of the lung is the most common malignancy causing SIADH but many other cancers can cause SIADH.

   4. Postoperative, 7–11%

   5. Drugs, 8–18%: Carbamazepine (20–30% of patients), oxcarbazepine, Ecstasy, ADH analogs (vasopressin, DDAVP, oxytocin [5% of patients]), chlorpropamide, NSAIDs, antidepressants (tricyclics and selective serotonin reuptake inhibitors), antipsychotics, cyclophosphamide, vincristine, nicotine, opioids, clofibrate, and many other medications

   6. AIDS

      1. SIADH may be secondary to a variety of AIDS complications including Pneumocystis pneumonia, CNS infections, or cancer.

      2. Hyponatremia may also develop secondary to HIV-related adrenal insufficiency or diarrhea (with free water ingestion).

   Evaluate patients with HIV and hyponatremia for adrenal insufficiency.

   7. Temporal arteritis

   8. Idiopathic

5. Reset osmostat

   1. A variant of SIADH in which ADH control is modulated to maintain serum sodium levels but at a lower range than normal. Patients retain their ability to excrete water load at that new equilibrium point.

   2. Therefore, hyponatremia is not progressive.

   3. Patients typically have serum sodium levels between 125 mEq/L and 135 mEq/L.

   4. Very dilute urine osmolality may be seen following water load (< 100 mOsm/L).

   5. Etiology is similar to SIADH.

   6. Treatment is directed at the underlying disorder.

EVIDENCE-BASED DIAGNOSIS

1. Standard criteria

   1. Effective serum osmolality is low (< 275 mOsm/L). This can be calculated using the following equation: Effective osmolality = (2 × Na⁺) + (Glucose/18).

   2. Urine sodium is typically > 30 mEq/L in patients with a normal dietary intake of sodium. (Since patients are typically euvolemic, there is no stimulus to avidly reabsorb sodium and it is excreted.) However, patients with a low dietary intake of sodium (13–42% of patients) may have a low urine sodium and low FE_Na.

   3. Urine osmolality is inappropriately not maximally dilute. Urine osmolality > 100 mOsm/L and usually > 300 mOsm/L. (ADH leads to water reabsorption in the tubules, concentrating the urine.)

   4. Patients are not using diuretics.

   5. Patients are clinically euvolemic.

   6. Other causes of euvolemic hyponatremia must be excluded (hypothyroidism, psychogenic polydipsia, secondary adrenal insufficiency).

      1. Secondary adrenal insufficiency can cause euvolemic hyponatremia and mimic SIADH.

      2. Despite recommendations to rule out adrenal insufficiency in patients with suspected SIADH, only 33–41% of patients are appropriately evaluated for adrenal insufficiency.

      3. Secondary adrenal insufficiency is diagnosed in 3–4% of patients in whom SIADH is initially suspected. (In 59% of patients, the secondary adrenal insufficiency was due to exogenous steroid use.)

TREATMENT