Diabetes insipidus
Diabetes insipidus affects about three out of 100,000 persons. This disorder is caused by a deficiency or ineffectiveness of vasopressin (ADH). It can be transient or chronic. Diabetes insipidus is characterized by excretion of excessive quantities of dilute urine and excessive thirst due to a compromised ability to conserve free water. Diabetes insipidus is easily distinguished from other causes of polyuria by the absence of a solute load (particularly glucose) and an abnormally low urine concentration.
Two types of diabetes insipidus are recognized: neurogenic (central) and nephrogenic (peripheral) (Table 4). Many underlying conditions can produce diabetes insipidus (Table 5). The most common form is neurogenic diabetes insipidus and is classified as either idiopathic or secondary to an intracranial event. Causes of diabetes insipidus in adults include idiopathic (25 percent), benign brain tumors (20 percent), blunt head trauma (17 percent), neurosurgery (9 percent), metastatic cancer (8 percent), and ischemic or toxic brain injury (6 percent). In contrast, only 8 percent of diabetes insipidus in children is idiopathic. The most common causes of childhood cases are tumors, neurosurgery, trauma, and meningitis. Idiopathic diabetes insipidus is invariably permanent and more often affects males.
Patients with diabetes insipidus present with marked polyuria and associated persistent thirst and polydipsia. These symptoms are usually well tolerated. Nocturia, or enuresis in children, is often the presenting complaint.
In contrast to nephrogenic diabetes insipidus, neurogenic diabetes insipidus is usually quite abrupt and often associated with a precipitating event. Pregnancy can exacerbate milder forms of diabetes insipidus; polyuria and polydipsia often improve postpartum in these cases. Lactation can stimulate ADH, causing some women with mild cases to show less intense symptoms when nursing.
Evaluation and Diagnosis. Other than a tow urine specific gravity, diabetes insipidus is not associated with any abnormality on physical examination or routine laboratory testing. Severe disturbances in hydration occur infrequently and are usually found in patients who are comatose, lack a normal thirst mechanism, or are too young to regulate their own water intake.
A water deprivation test is used to confirm the presence of diabetes insipidus and to differentiate between neurogenic
Table 4
Classification of Diabetes Insipidus
Cause Type
Decreased arginine vasopressin Neurogenic
(AVP) secretion Cranial
Central
Hypothalamic
Vasopressin-responsive
Decreased AVP effect Nephrogenic
Vasopressin-resistant
Excessive water intake Primary polydipsia
Increased AVP metabolism Gestational
Table 5
Causes of Diabetes Insipidus
Neurogenic causes
Idiopathic
Acquired
Neoplastic: craniopharyngioma, lymphoma, meningioma, metastatic carcinoma, other brain tumor
Head trauma
Neurosurgery
Ischemia: shock, cardiac arrest, Sheehan’s syndrome (postpartum pituitary necrosis), Aneurysm, sickle cell crisis
Granulomatosis
Sarcoidosis, histiocytosis
Infectious: tuberculosis, encephalitis, meningitis
Autoirnrnune
Familial
Nephrogenic causes
Familial
Acquired
Drug-induced: lithium, demeclocycline (Declornycin), methoxyflurane (Penthrane)
Metabolic: hypokalemia, hypercalciuria, usually with hypercalcemia Renal disease: polycystic kidney disease, obstructive uropathy, chronic pyelonephritis, sickle cell nephropathy, sarcoidosis, chronic renal failure, multiple myeloma, Sjogren’s disease, analgesic nephropathy
and nephrogenic forms. A mild form of dehydration is induced in a controlled fashion, with hourly monitoring of urine osmolality and specific gravity and serum sodium and osmolality. Adequate dehydration is documented by a weight loss of 1.3 to 2.25 kg (3.0 to 5.0 lb) in adults or two successive urine osmolality values that differ by less than 30 mOsm per kg in children, indicating that a maximum concentration steady state has been reached. The serum ADH level is then determined, and the patient is given S units of ADH subcutaneously. Urine and serum osmolality values are determined at hourly intervals for several hours.
The key to diagnosing diabetes insipidus and distinguishing between neuro-genie and nephrogenic forms lies not in the absolute test results, but in the ADH level and the association between urine and serum osmolality in response to dehydration (Table 6). The water deprivation test is so accurate that direct measurement of ADH is frequently not necessary.
A closely monitored trial of desmopressin (DDAVP) also may be used to diagnose diabetes insipidus. The patient has neurogenic diabetes insipidus if a standard treatment with DDAVP (2 to 4 meg subcutaneously every 12 hours for two days) resolves the polydipsia and polyuria without causing water intoxication.
If a patient is diagnosed with neurogenic diabetes insipidus, the underlying cause must be determined. In patients who are otherwise asymptomatic, MRI of the head is used to detect possible hypo-thalamic tumors. MRI is thought to be 80 to 95 percent sensitive in detecting microadenomas; CT is slightly less sensitive.
Treatment. Patients with neurogenic diabetes insipidus are treated with intranasal DDAVP (Stimate®). DDAVP, a synthetic analog of vasopressin without pressor or uterine effects, is the formulation of ADH that is best tolerated, easiest to administer, and most consistent in its antidiuretic effect. The duration of relief ranges from eight to 20 hours and varies between patients, but remains constant within individuals.
A starting dose of 10 meg at night is usually sufficient to relieve nocturia; a morning dose may be added if symptoms persist during the day. The actual dose delivered can be titrated by using a special nasal catheter. DDAVP is expensive; a 50-dose bottle costs $100. Patients should be encouraged to undertreat themselves to guard against volume overload and hyponatremia.
Laboratory Tests for the Differential Diagnosis of Diabetes Insipidus
Urine osmolality one hour
after subcutaneous
Urine specific Urine osmolality Plasma osmolality administration of 5 mL
Type gravity (mOsm per kg) (mOsm per kg) aqueous ADH
Normal Greater than or 700 to 1,400 285 to 295 No change
equal to 1.015
Central diabetes Less than 1.010 50 to 200 310 to 320 Doubles
insipidus (complete)
Central diabetes 1.010 to 1.01 250 to 500 295 to 305 Increases
insipidus (partial)
Nephrogenic Less than 1.010 100 to 200 310 to 320 No change
diabetes insipidus
Patients with partial diabetes insipidus may respond to chlorpropamide (Diabinese), a hypoglycemic drug that stimulates ADH secretion and potentiates its effects on the kidneys. Clofibrate (Atromid-S) and carbamazepine (Atretol, Epitol, Tegretol) may also stimulate ADH secretion and may be used to treat patients with partial diabetes insipidus.
ADH replacement is ineffective in patients with nephrogenic (peripheral) diabetes insipidus. Certain drugs improve polyuria and, thus, reduce polydipsia. Diuretics, such as thiazides or amiloride (Midamor), or both, function by depleting total body salt, increasing the isotonic absorption of water in the proximal tubule. However, a diet heavy in salt can counter this effect. Most patients respond to a daily dose of hydrochlorothiazide (Esidrix, HydroDIURIL, Hydro-Par), 50 to 100 mg.