Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (226 page)

   Laboratory Findings

  1.  Measurement of urine output. To confirm the presence of polyuria, one can collect a 24-hour urine specimen or the patient can keep a diary for 24 hours, recording the volume and the time of each voided urine.

  2.  Serum sodium and urine osmolality. A low serum sodium concentration (<137 mEq/L) with a low urine osmolality (e.g., less than one-half the plasma osmolality) is usually indicative of water overload due to primary polydipsia. A high-normal serum sodium concentration (>142 mEq/L) points toward DI, particularly if the urine osmolality is less than the plasma osmolality. A normal serum sodium concentration is not helpful in diagnosis but, if associated with a urine osmolality more than 600 mOsm/kg, excludes a diagnosis of DI. Hypernatremia during the first year of life is a common feature in children with hereditary nephrogenic DI.

  3.  Water deprivation test (also known as water restriction test). This test is important to differentiate the major forms of DI. Each of the causes of DI produces a distinct pattern to water deprivation and desmopressin (dDAVP) administration. Complete central DI is associated with urine osmolality <200 mOsm/kg after deprivation and marked increase (more than 100%) in urine osmolality after dDAVP administration. Partial central DI shows urine osmolality between 200 and 800 mOsm/kg after deprivation and variable increase (15–50%) in urine osmolality after dDAVP administration. Nephrogenic DI demonstrates submaximal rise in urine osmolality (usually below 300 mOsm/kg) after deprivation and little or no elevation in urine osmolality after dDAVP administration. Primary polydipsia is associated with a rise in urine osmolality (usually above 500 mOsm/kg) after water deprivation and no response to dDAVP administration.

Water deprivation tests for older infants and children should be performed in the hospital under close medical supervision. The patient should not be allowed to lose more than 5% of his or her body weight.

Water deprivation is not performed in newborns or very young infants suspected to have hereditary nephrogenic DI. The preferred diagnostic test in this setting is the administration of dDAVP with the measurement of the urine osmolality at baseline and at 30 minutes over the next 2 hours. If the urine osmolality does not increase by more than 100 mOsm/kg over baseline, the diagnosis of nephrogenic DI is made and DNA should be obtained for mutation analysis.

  4.  Plasma ADH measurement. When results of water deprivation test are ambiguous, plasma ADH assay is a useful adjunct. Plasma samples collected at baseline and following water deprivation (prior to the administration of ADH) should be sent for the measurement of ADH. Baseline plasma ADH should be low in patients with central DI and high in patients with nephrogenic DI. Primary polydipsia can associate with normal or low plasma ADH. If there is an increase in plasma ADH in response to the rising urine osmolality, central DI is excluded. If there is an appropriate elevation in urine osmolality and plasma ADH rises, nephrogenic DI is excluded.

  5.  Solute diuresis needs to be differentiated from DI. Solute diuresis is a form of polyuria in which large amount of filtered, nonreabsorbable solute gain entry to the renal tubules. The most common clinical example of solute diuresis is glycosuric diuresis seen in diabetic hyperglycemia. The urine osmolality in a solute diuresis is usually above 300 mOsm/kg, in contrast to the dilute urine typically found with a water diuresis seen in DI. Total solute excretion (calculated on a 24-hour urine collection from the product of the urine osmolality and the urine volume) is normal with a water diuresis (600–900 mOsm/day) but markedly increased with a solute diuresis.

Suggested Readings

Bichet DG. Clinical manifestations and causes of central diabetes insipidus. In: Rose B, (ed).
UpToDate
, Waltham, MA: UpToDate, Inc.; 2009.

Bichet DG. Clinical manifestations and causes of nephrogenic diabetes insipidus. In: Rose B, (ed).
UpToDate
, Waltham, MA: UpToDate, Inc.; 2009.

Bichet DG. Diagnosis of polyuria and diabetes insipidus. In: Rose B, (ed).
UpToDate
, Waltham, MA: UpToDate, Inc.; 2009.

Khan F, Sachs H, Pechet L, et al.
Guide to Diagnostic Testing
. Philadelphia, PA: Lippincott Williams & Wilkins; 2002.

Kronenberg HM, Melmed S, Polonsky KS, et al.
Williams Textbook of Endocrinology
, 11th ed. Philadelphia, PA: Saunders, Elsevier Inc.; 2008.

SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION

   Definition

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder in which ADH release is either autonomous or poorly regulated. SIADH results when plasma levels of ADH are elevated and when the physiologic secretion of ADH from the posterior pituitary would normally be suppressed.

   Overview

SIADH is the most common cause of euvolemic hypoosmolality, and it is also the single most common cause of hypoosmolality encountered in clinical practice. It accounts for 20–40% among all hypoosmolar patients.

   Common Causes

  1.  Tumors. Ectopic production of ADH by a tumor is most often due to a small cell carcinoma of the lung but is also occasionally seen with other lung tumors. Less common causes include carcinomas of the pancreas, duodenum, prostate, and head and neck.

  2.  CNS disorders. A large number of different CNS disorders including stroke, hemorrhage, infection, trauma, and psychosis can enhance ADH release.

  3.  Drugs. Various drugs can lead to SIADH, and they include antineoplastic agents (vincristine, cyclophosphamide), antidepressant drugs (amitriptyline, phenothiazines), serotonin reuptake inhibitors (fluoxetine, sertraline), chlorpropamide, carbamazepine, oxcarbazepine, and clofibrate.

  4.  Pulmonary diseases. Infectious diseases such as tuberculosis, bacterial and viral pneumonia, aspergillosis, and empyema can lead to the SIADH. A similar response may occasionally be seen with asthma, atelectasis, acute respiratory failure, and pneumothorax.

  5.  HIV infection

  6.  Major surgery. Major abdominal or thoracic surgery is often associated with transient hypersecretion of ADH.

  7.  Hormone deficiency. Both adrenal insufficiency and hypothyroidism may be associated with hyponatremia and SIADH, which can be corrected by hormone replacement.

  8.  Idiopathic. Some patients appear to have idiopathic SIADH, with a higher rate in the elderly.

   Who Should Be Suspected?

The hallmark of SIADH is hypoosmolality. Clinical manifestations of hypoosmolality are mainly a broad spectrum of neurologic symptoms, ranging from mild nonspecific symptoms (e.g., headache, nausea) to more significant disorders (e.g., disorientation, confusion, obtundation, focal neurologic deficits, and seizures). This neurologic symptom complex has been known as hyponatremic encephalopathy. Nonneurologic symptoms are relatively uncommon.

Clinical euvolemia is usually present, and it is defined by the absence of signs of hypovolemia (orthostasis, tachycardia, decreased skin turgor, dry mucous membranes) or hypovolemia (subcutaneous edema, ascites).

   Laboratory Findings

  1.  Decreased plasma osmolality

  2.  Hyponatremia

  3.  Inappropriately elevated urine osmolality (above 100 mOsm/kg and usually above 300 mOsm/kg)

  4.  Elevated urine sodium concentration (usually above 40 mEq/L)