Syndrome of inappropriate secretion of ADH (SIADH)

SIADH is defined as continued secretion of antidiuretic hormone (ADH) despite a low serum osmolality. The diagonsis of SIADH can only be made when there is a normal state of hydration; normal renal, thyroid, and adrenal function; and when the patient is not taking diuretics. In all instances of excess ADH secretion, patients have abnormally low concentrations of sodium ions in their blood (a condition known as hyponatremia). A low serum sodium may result from salt losses or from an excess amount of water in the bloodstream.

Arginine vasopressin is produced by the posterior pituitary gland. It acts upon the kidneys to cause them to retain water. This is a very important mechanism to prevent dehydration. Too much vasopressin can cause the kidneys to hold too much water, diluting out the sodium level in the bloodstream.

Possible causes of SIADH include ADH secretion from malignant systemic tumors (for example, small cell lung carcinoma, lymphoma, and pancreatic tumors) or chronic obstructive pulmonary disease. SIADH can also be induced by drugs such as phenothiazine, tricyclic antidepressants, carbamazepine, and lithium. Central nervous system disorders can be associated with SIADH, perhaps through loss of chronic inhibition of the brain on the hypothalamic neurons.

SIADH occurs after pituitary surgery in approximately 10% of patients. This disorder is more common in patients with Cushing’s disease after surgery (approximately 20% of patients undergoing surgery for Cushing's disease will have postoperative hyponatremia). The time course of development of postoperative hyponatremia after pituitary surgery varies between three and seven days. Some patients have a period of diabetes insipidus prior to developing hyponatremia. The disorder may last 3 to 10 days. Usually, it is followed by recovery of normal osmoregulation but some patients develop diabetes insipidus after the period of hyponatremia.

Symptoms

Symptoms and signs of acute hyponatremia after surgery include worsening headache, nausea, and flulike symptoms. The symptoms are largely attributed to cerebral edema, or swelling of the brain. Severe cases may be associated with confusion, excessive sleepiness, and even coma. This disorder is potentially fatal. Early recognition and prompt treatment are of paramount importance.

Treatment

Most patients with postoperative hyponatremia should be hospitalized for observation and management. The drug tolvaptan is used to block vasopressin’s action on the vasopressin receptor in the kidney. Treatment with this drug normalizes serum sodium concentrations in most patients with postoperative hyponatremia and symptoms resolve quickly. Historically patients were treated for hyponatremia by severely restricting fluid intake while observing them in the hospital until the hyponatremia resolved. However, treatment with tolvaptan shortens the time spent in the hospital for observation.