SIADH is a syndrome resulting from the abnormal production of antidiuretic hormone (ADH), causing excessive water retention, dilutional hyponatremia, and increased excretion of sodium.

A. Normally, the primary function of ADH is to retain water when the body needs it. Its release is regulated by a negative feedback mechanism.

B. Without the presence of ADH, one would need to ingest 10 to 20 L of water per day to match urinary losses.

C. ADH is released by the posterior pituitary in response to increased plasma osmolality or decreased plasma volume.

D. ADH causes increased water reabsorption at the distal renal tubules and collecting ducts, thereby diluting the blood and returning plasma osmolality to normal levels.

E. Ectopic (outside of the pituitary gland) ADH does not follow this normal feedback mechanism and is released uncontrollably, leading to excess ADH and chronically diluted blood.

F. The predominant etiology of clinical symptoms with this disorder is related to its hyponatremia.

1. Normal sodium levels are 135 to 145 mEq/L.

2. Sodium is the primary electrolyte in the extracellular fluid.

3. Severe hyponatremia of acute onset leads to cellular swelling, which can have dangerous consequences if left untreated.

A. Cancer is the most frequent cause of ectopic ADH production. This abnormal production of ADH confuses the body into believing that it needs to hold onto more water. Small-cell lung cancer is responsible for the majority of SIADH cases (80%). Other cancers that are associated with SIADH include the tumors of the pancreas, prostate, brain, lymphatic system, and duodenum. Any tumor that can metastasize to the lungs can also cause SIADH (see C. below).

B. Central nervous system disease, such as meningeal infection or brain tumors, may also trigger SIADH due to its direct or indirect effects on the pituitary gland.

C. Pulmonary conditions, such as tuberculosis (TB), chronic obstructive pulmonary disease (COPD), lung abscesses, or pneumonia and positive pressure ventilation can stimulate ADH receptors in the lungs, causing the release of ADH.

D. Drugs that most notably induce or potentiate SIADH include the thiazide diuretics, antidepressants, antipsychotics, morphine, and oral hypoglycemic agents. Antineoplastics agents such as vincristine, cisplatin, bleomycin, and cyclophosphamide have also been associated with this syndrome.

A. Assessment

1. The severity of symptoms greatly depends on the onset of sodium depletion and severity of the water retention (Table 39-1).

a. Acute onset SIADH with sodium levels

b. Patients with chronic SIADH may be asymptomatic despite sodium levels

2. Hyponatremia occurs because of increased water reabsorption at the distal renal tubules, thereby diluting the contents of the blood and increasing the concentration of sodium in the urine. This results in decreased serum osmolality, increased urinary osmolality, and the development of cellular swelling (cellular water intoxication). Clinical manifestations of SIADH are usually related to one of three mechanisms.

a. Cellular swelling and cerebral edema. Signs and symptoms include:

(1) Confusion

(2) Irritability

(3) Headache

(4) Muscle weakness cramps

(5) Lethargy

(6) Seizures

(7) Coma

(8) Death

b. Increased water reabsorption occurs because of abnormal ADH production, which stimulates increased water reabsorption at the distal renal tubules. Signs and symptoms include:

(1) Decreased urine output

(2) Weight gain

(3) Increased specific gravity

(4) Edema

c. Decreased gastrointestinal motility occurs because of hyponatremia and fluid imbalance. Signs and symptoms include:

(1) Nausea and vomiting

(2) Anorexia

B. Diagnostic Criteria (Table 39-2)

1. Serum tests

a. Serum sodium is decreased due to renal sodium loss and serum dilution by inappropriate water reabsorption.

b. Serum osmolality is decreased due to inappropriate water reabsorption.

c. BUN and creatinine are normal.

d. Potassium, calcium, and magnesium are decreased due to dilution from inappropriate water reabsorption.

2. Urine tests

a. Urine sodium is increased due to normal renal perfusion and excretion of sodium despite decreased serum sodium.

b. Urine osmolality is increased due to water reabsorption at the tubules despite decreased serum osmolality.

c. Urine specific gravity is increased above the normal range of 1.002 to 1.028 due to less water and higher levels of solutes. Specific gravity measures the kidney’s ability to concentrate or dilute urine in relation to plasma. Because urine is a solution containing minerals, salts, and compounds dissolved in water, the normal specific gravity is greater than 1.000. The more concentrated the urine, the higher the urine specific gravity.