This is another syndrome involving AVP (ADH) that is now well recognized. It results from water retention due to secretion of AVP (ADH) when AVP (ADH) would not ordinarily be secreted. The criteria for IADH syndrome include (1) hyponatremia, (2) continued renal excretion of sodium despite hyponatremia, (3) serum hypoosmolality, (4) urine osmolality that shows a significant degree of concentration (instead of the maximally dilute urine one would expect), (5) no evidence of blood volume depletion, and (6) normal renal and adrenal function (this criterion is necessary to rule out continuous sodium loss due to renal disease or Addison’s disease; diuretic-induced urine sodium loss should also be excluded). These criteria attempt to demonstrate that AVP (ADH) is secreted despite hemodilution, decreased serum osmolality, or both. The reason for increased sodium excretion is not definitely known; it is thought that increase of interstitial fluid volume by water retention may lead to suppression of sodium reabsorption (in order not to reabsorb even more water). Most patients with IADH syndrome do not have edema, since interstitial fluid expansion is usually only moderate in degree.

In the diagnosis of IADH syndrome a problem may arise concerning what urine osmolality values qualify as a significant degree of concentration. If the serum and urine specimens are obtained at about the same time and the serum demonstrates significant hyponatremia and hypoosmolality, a urine osmolality greater than the serum osmolality is considered more concentrated than usual. However, in some cases of IADH syndrome the urine need not be higher than the serum osmolality for the diagnosis to be made, if it can be demonstrated that water retention is taking place despite a hypotonic plasma. With significant serum hypoosmolality, urine osmolality should be maximally dilute. This value is about 60-80 milliosmoles (mOsm)/L. A urine osmolality greater than 100 mOsm/L (literature range, 80-120 mOsm/L) can be considered a higher osmolality than expected under these circumstances. The urine sodium level is usually more than 20 mEq/L in patients with IADH syndrome, but can be decreased if the patient is on sodium restriction or has volume depletion. In patients with borderline normal or decreased urine sodium levels, the diagnosis of IADH may be assisted by administering a test dose of sodium. In IADH syndrome, infusion of 1,000 ml of normal saline will greatly increase urine sodium excretion but will not correct the hyponatremia as long as the patient does not restrict fluids (fluid restriction will cause sodium retention in IADH syndrome). Water restriction is the treatment of choice and may provide some confirmatory evidence. However, water restriction is not diagnostic, since it may also benefit patients with extracellular fluid (ECF) excess and edema. Uric acid renal clearance is increased in IADH syndrome, resulting in decreased serum uric acid levels in most, but not all, patients. Decreased serum uric acid levels in a patient with hyponatremia is another finding that is nondiagnostic but that raises the question of IADH syndrome.

In some patients, assay of serum AVP (ADH) levels may be helpful to confirm the diagnosis. The AVP (ADH) levels should be elevated in IADH syndrome. However, AVP (ADH) assay is expensive, technically very difficult, and is available only in a few reference laboratories. The specimen should be placed immediately into a precooled anticoagulant tube, centrifuged at low temperature, frozen immediately, and sent to the laboratory packed in dry ice.

IADH syndrome may be induced by a variety of conditions, such as: (1) central nervous system neoplasms, infections, and trauma; (2) various malignancies, most often in bronchogenic carcinoma of the undifferentiated small cell type (11% of patients); (3) various types of pulmonary infections; (4) several endocrinopathies, including myxedema and Addison’s disease; (5) certain medications, such as antineoplastics (vincristine, cyclophosphamide), oral antidiabetics (chlorpropamide, tolbutamide), hypnotics (opiates, barbiturates), and certain others such as carbamazepine; and (6) severe stress, such as pain, trauma, and surgery.

Normal physiologic response to surgery is a temporary moderate degree of fluid and electrolyte retention, occurring at least in part from increased secretion of AVP (ADH). In the first 24 hours after surgery there tends to be decreased urine output, with fluid and electrolytes remaining in the body that would normally be excreted. Because of this, care should be taken not to overload the circulation with too much IV fluid on the first postoperative day. Thereafter, adequate replacement of normal or abnormal electrolyte daily losses is important, and excessive hypotonic fluids should be avoided. In certain patients, such as those undergoing extensive surgical procedures and those admitted originally for medical problems, it is often useful to obtain serum electrolyte values preoperatively so that subsequent electrolyte problems can be better evaluated.