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Diagnosis of polyuria and diabetes insipidus

Author:
Daniel G Bichet, MD Section
Editors:
Richard H Sterns, MD
Michael Emmett, MD Deputy
Editor:
John P Forman, MD, MSc

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Jan 2018. | This topic last updated: Sep 28,
2017.

DEFINITION — Polyuria has generally been defined as a urine output exceeding 3

L/day in adults and 2 L/m2 in children. It must be differentiated from the more
common complaints of frequency or nocturia, which are not associated with an
increase in the total urine output.

The following is an overview of the diagnosis of polyuria and diabetes insipidus (DI).
The causes and treatment of polyuria due to central or nephrogenic DI are presented
separately. (See "Clinical manifestations and causes of central diabetes insipidus" and
"Clinical manifestations and causes of nephrogenic diabetes insipidus" and "Treatment
of central diabetes insipidus" and "Treatment of nephrogenic diabetes insipidus".)

CAUSES — In the absence of a glucose-induced osmotic diuresis in uncontrolled

diabetes mellitus, there are three major causes of polyuria in the outpatient setting,
each of which is due to a defect in water balance leading to the excretion of large
volumes of dilute urine (urine osmolality usually below 250 mosmol/kg): primary
polydipsia, which is primarily seen in adults and adolescents; central DI; and
nephrogenic DI [1].

Primary polydipsia — Primary polydipsia (sometimes called psychogenic polydipsia)

is characterized by a primary increase in water intake. This disorder is most often seen
in middle-aged women and in patients with psychiatric illnesses, including those taking
a phenothiazine, which can lead to the sensation of a dry mouth. Primary polydipsia
can also be induced by hypothalamic lesions that directly affect the thirst center, as
may occur with an infiltrative disease such as sarcoidosis [1]. (See "Causes of
hyponatremia in adults".)

Central DI — Central DI (also called neurohypophyseal or neurogenic DI) is associated

with deficient secretion of antidiuretic hormone (ADH). This condition is most often
idiopathic (possibly due to autoimmune injury to the ADH-producing cells) or can be
induced by trauma, pituitary surgery, or hypoxic or ischemic encephalopathy. Rare

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familial cases have been described [2]. (See "Clinical manifestations and causes of
central diabetes insipidus".)

Nephrogenic DI — Nephrogenic DI is characterized by normal ADH secretion but

varying degrees of renal resistance to its water-retaining effect. This problem, in its mild
form, is relatively common since most patients who are older adults or who have
underlying renal disease have a reduction in maximum concentrating ability. This
defect, however, is not severe enough to produce a symptomatic increase in urine
output.

Symptomatic polyuria due to ADH resistance is seen primarily in four settings, all of
which are discussed in detail elsewhere (see "Clinical manifestations and causes of
nephrogenic diabetes insipidus"):

●Nephrogenic DI presenting in childhood is almost always due to inherited

defects. The most common are X-linked hereditary nephrogenic DI due to
mutations in the AVPR2 gene encoding the ADH receptor V2 and autosomal
recessive and dominant nephrogenic DI due to mutations in the aquaporin-2
(water channel) gene.

●Nephrogenic DI presenting in adults is almost always acquired with chronic

lithium use and hypercalcemia being the most common causes of a defect severe
enough to produce polyuria.

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS — In addition to nephrogenic and

central DI, a variety of conditions may result in the complaint of polyuria, including
psychogenic polydipsia, prostatic hypertrophy, or osmotic diuresis (including
postobstructive diuresis). (See "Clinical manifestations and diagnosis of urinary tract
obstruction and hydronephrosis", section on 'Prognosis and recovery of renal function'.)

The cause of polyuria is often suggested from the history (eg, age of onset and eliciting
the possible presence of the different causes of DI) and, rarely, by the plasma sodium
concentration. Specific testing is then performed to establish the diagnosis.

Onset of polyuria — The patient (or their parent) should be questioned about the rate
of onset of the polyuria. In the majority of cases of hereditary nephrogenic DI, severe
polyuria (with risk of dehydration and hypernatremia) manifests during the first week of
life. In familial central DI (usually an autosomal dominant disease), polyuria may
present after the first year of life, sometimes in young adulthood, due to preservation of
function of the normal allele [3]. (See "Clinical manifestations and causes of
nephrogenic diabetes insipidus" and "Clinical manifestations and causes of central
diabetes insipidus".)

In adults, the onset is usually abrupt in central DI ("I suddenly began urinating too much
a few days ago") and almost always gradual in acquired nephrogenic DI or primary
polydipsia.

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The new onset of nocturia in the absence of other causes of nocturia (eg, prostatic
enlargement in men over 50 years of age or urinary tract infection in children) is often a
first clue to DI. The urine is normally most concentrated in the morning due to lack of
fluid ingestion overnight; as a result, the first manifestation of a loss of concentrating
ability is often nocturia.

Family history — There are familial forms of both central and nephrogenic DI. The
defects in these disorders are due to mutations that impair antidiuretic hormone (ADH)
synthesis or the renal response to ADH; the latter defect is most often due to mutations
in the AVPR2 gene encoding the V2 receptor but can also result from mutations in the
aquaporin-2 (water channel) gene [4]. A family history of polyuria is helpful both for
diagnosis and to identify asymptomatic members of affected families who harbor the
suspect allele. Thus, all families with hereditary DI should have their molecular defect
identified. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus"
and "Clinical manifestations and causes of central diabetes insipidus".)

Plasma sodium and urine osmolality — Each of the three causes of polyuria,
primary polydipsia, central DI, and nephrogenic DI, is associated with an increase in
water output and the excretion of a relatively dilute urine. With primary polydipsia, the
polyuria is an appropriate response to enhanced water intake; by comparison, the
water loss is inappropriate with either form of DI. Measurement of the plasma sodium
concentration and the urine osmolality may be helpful in distinguishing between these
disorders:

●A low plasma sodium concentration (less than 137 mEq/L) with a low urine
osmolality (eg, less than one-half the plasma osmolality) is usually indicative of
water overload due to primary polydipsia.

●A high-normal plasma sodium concentration (greater than 142 mEq/L, due to

water loss) points toward DI, particularly if the urine osmolality is less than the
plasma osmolality [1].

●A normal plasma sodium concentration is not helpful in diagnosis but, if

associated with a urine osmolality more than 600 mosmol/kg, excludes a
diagnosis of DI.

In adults with DI and no cognitive impairment, true hypernatremia (plasma sodium

concentration greater than 150 mEq/L) should not occur, because the initial loss of
water stimulates thirst, resulting in an increase in intake to match the urinary losses
(figure 1).

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An exception to this general rule occurs in adipsic DI. Adipsic DI is usually due to a
central lesion that also impairs thirst, thereby causing hypodipsia or adipsia; in this
setting, the plasma sodium concentration can exceed 160 mEq/L [5]. Adipsic DI is
associated with significant morbidity including obesity, sleep apnea, venous thrombosis
during episodes of hypernatremia, thermoregulatory dysfunction, seizures, and
significant mortality [6].

Adipsic DI accompanied by autoantibodies to the subfornical organ was described in a

small case series of young patients with hypernatremia, no thirst, and low vasopressin
response to hypertonicity [7]. In contrast to classical cases of adipsic DI, in which
structural abnormalities of the hypothalamic area are easily seen with magnetic
resonance imaging, no such lesions were identified in these cases. Sera from all four
patients contained circulating antibodies that reacted to the subfornical organ in mice,
and injection of immunoglobulin from one of the patients produced similar clinical
abnormalities in mice.

Withholding water (eg, for diagnostic or surgical procedures) in adults with DI can result
in severe dehydration. Thus, if oral intake has to be withheld, the patient should be
hospitalized and hydrated intravenously and the plasma sodium concentration closely
monitored while intake is restricted.

Hypernatremia during the first year of life is a common feature in children with
hereditary nephrogenic DI. The intense and constant thirst of these young children is
often not understood by adults, particularly if this is the first affected family member due
to a de novo mutation or if an X-linked mutation has passed unrecognized through
asymptomatic females [8].

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Measurement of urine output — The value of obtaining a timed urine collection to
confirm the presence of polyuria is uncertain. Potential problems include an incomplete
collection and the necessity for multiple containers if the patient has severe polyuria,
which can be minimized by obtaining an 8-hour rather than a 24-hour collection.
Measurement of urinary creatinine excretion can help determine if the collection is
complete. (See "Assessment of kidney function", section on 'Limitations of using
creatinine clearance'.)

Water restriction test — Even if the history and/or plasma sodium concentration and
urine osmolality appear to be helpful, the diagnosis should be confirmed by raising the
plasma osmolality either by water restriction or, less commonly in adults, by the
administration of hypertonic saline (0.05 mL/kg per min for no more than two hours).
The administration of hypertonic saline is typically reserved for use if the water
restriction test is inconclusive or cannot be performed. A water restriction test to
exclude primary polydipsia is not necessary if the plasma sodium concentration is
greater than 145 mEq/L and the urine osmolality is less than the plasma osmolality [9].

Water restriction is important to differentiate central DI from primary polydipsia; simply

giving exogenous ADH (desmopressin is generally preferred to aqueous vasopressin)
without water restriction will not distinguish between these two conditions, since both
have submaximal plasma ADH levels and both will respond to desmopressin therapy.
However, a water restriction test may not be necessary prior to desmopressin
administration.

Exceptions to this general rule are patients with a dilute urine (ie, urine osmolality well
below that of the plasma) who are strongly suspected of having nephrogenic DI (eg,
long-term lithium use) and newborns and young infants who are thought to have
hereditary nephrogenic DI. In these patients who are resistant to ADH, the response to
desmopressin can be evaluated without prior water restriction. (See 'Infants and
children' below.)

The diagnostic approach is also different in patients with DI and a defect in thirst who
present with overt hypernatremia. (See "Etiology and evaluation of hypernatremia in
adults".)

The normal physiologic response to the water restriction test (or the administration of
hypertonic saline) is based upon the following observations [1,10,11]:

●Raising the plasma osmolality leads to a progressive elevation in ADH release

and an increase in urine osmolality in normal individuals (figure 1).

●Once the plasma osmolality reaches 295 to 300 mosmol/kg (normal 275 to
290 mosmol/kg) or the plasma sodium is 145 mEq/L or higher, the effect of
endogenous ADH on the kidney is maximal. At this point, administering
desmopressin will not further elevate the urine osmolality unless endogenous
ADH release is impaired (ie, unless the patient has central DI).

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Adults — The water restriction test for the evaluation of polyuria involves
measurement of the urine volume and osmolality every hour and the plasma sodium
concentration and osmolality every two hours. We generally recommend that the
patient stop drinking two to three hours before coming to the office or clinic; overnight
fluid restriction should be avoided since potentially severe volume depletion and
hypernatremia can be induced in patients with marked polyuria. As an example, we
saw a patient with undiagnosed DI who was scheduled for surgery in the morning and
was told to stop drinking and eating after going to sleep the night before. Surgery was
cancelled when routine preoperative laboratory testing revealed a plasma sodium of
162 mEq/L.

The water restriction test in adults is continued until one of the following end points is
reached:

●The urine osmolality reaches a clearly normal value (above

600 mosmol/kg), indicating that both ADH release and effect are intact. Patients
with partial DI may have a substantial rise in urine osmolality but not to this extent.

●The urine osmolality is stable on two or three successive hourly measurements

despite a rising plasma osmolality.

●The plasma osmolality exceeds 295 to 300 mosmol/kg or the plasma sodium is
145 mEq/L or higher.

In the last two settings, desmopressin is administered (10 mcg by nasal insufflation or 4
mcg subcutaneously or intravenously) and the urine osmolality and volume monitored.
The urine osmolality and volume should be measured every 30 minutes over the next
two hours. The two-hour monitoring period is particularly important if there is dilatation
of the urinary bladder by previous high urine volumes. In this setting, any concentrated
new urine might be diluted with post-micturitional residual urine (which could be as
much as 200 to 400 mL).

Plasma and urine ADH levels should be measured if the response to the water
restriction test is equivocal. (See 'Plasma and urine ADH measurement' below.)

Copeptin, the C-terminal glycoprotein moiety of pro-arginine vasopressin (AVP), is a

stable surrogate marker of vasopressin secretion. Without prior water deprivation, a
single baseline copeptin level >21.4 picomol/L was found to differentiate nephrogenic
DI from other etiologies with 100 percent sensitivity and specificity, rendering water
deprivation testing unnecessary in such cases [12].

Infants and children — Water restriction is not performed in newborns or very young
infants suspected to have hereditary nephrogenic DI (eg, documented plasma sodium
145 mEq/L or higher with a concomitant urine osmolality ≤200 mosmol/kg). The
preferred diagnostic test in this setting is the administration of desmopressin (1 mcg
subcutaneously or intravenously infused over 20 minutes, maximum dose
0.4 mcg/kg of body weight) with measurement of the urine osmolality at baseline and at

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30-minute intervals over the next two hours. If the urine osmolality does not increase by
more than 100 mosmol/kg over baseline, the diagnosis of nephrogenic DI is made and
DNA should be obtained for mutation analysis [3].

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 percent of their body weight. Monitoring of vital signs (temperature, pulse,
and blood pressure), body weight, laboratory tests, urine and plasma osmolalities, and
the plasma sodium concentration are essential.

A recommended protocol includes the following steps:

●The test is performed after breakfast. It is started after the child voids or, in
infants, after the first spontaneous void after the morning feed. Body weight and
plasma sodium and osmolality are measured after the patient voids. No further
fluid is given until the test is terminated.

●Record each urine void and measure the urine volume, specific gravity, and
osmolality.

●Weight and vital signs are obtained every two hours for the first four hours and
then hourly. The plasma sodium and osmolality are measured at four hours and
then every two hours until the conclusion of the test.

The test is terminated when one of the following end points are attained:

●Urine specific gravity ≥1.020

●Urine osmolality is ≥600 mosmol/kg

●Plasma osmolality exceeds 295 or 300 mosmol/kg or plasma sodium is 145

mEq/L or higher

●The patient has lost 5 percent of body weight or exhibits signs of volume
depletion

●If the period of water restriction reaches six hours in infants less than six months
of age, eight hours in children from six months to two years of age, or 12 hours in
children older than two years of age

At the end of the test, weight, vital signs, plasma sodium, plasma and urine osmolality,
and urine specific gravity should be measured. A specimen should also be obtained for
measurement of plasma ADH, which is always elevated during short dehydration tests
in patients with hereditary nephrogenic DI.

Children who continue to have impaired urinary concentration despite reaching a

plasma osmolality of 295 mosmol/kg or a plasma sodium of 145 mEq/L can be given
desmopressin (5 to 10 mcg by nasal insufflation or 2 to 4 mcg intravenously or
subcutaneously). The urine volume and osmolality are measured to detect any

7
antidiuretic response. We no longer use aqueous vasopressin which, due to its
vasoconstrictive effect mediated by the V1a receptor, produces sudden and
noticeable pallor that raises concerns with the mother.

Interpretation — Accurate interpretation of the water restriction test usually requires

that desmopressin not be given before the urine osmolality has stabilized or the
plasma osmolality has reached 295 mosmol/kg. Below this level, maximum
endogenous ADH effect may not be present and an antidiuretic response to
desmopressin is of no diagnostic benefit, since it will raise the urine osmolality even in
normal subjects.

Each of the causes of polyuria produces a distinctive pattern to water restriction and
desmopressin administration [1,9-11]:

●Central DI is usually partial, and therefore both ADH release and the urine
osmolality may increase as the plasma osmolality rises but
submaximally. Desmopressin will lead to a rise in urine osmolality (and an
equivalent fall in urine output) of more than 100 percent in complete central DI and
15 to 50 percent in partial central DI [10,11].

●Nephrogenic DI is also associated with a submaximal rise in urine osmolality in

response to water restriction. The elevation in plasma osmolality stimulates ADH
release, which, since most patients with acquired nephrogenic DI are partially (not
completely) resistant to ADH, may induce a modest increase in urine osmolality.
The administration of exogenous desmopressin (which increases plasma levels 5-
to 10-fold) produces [10,11]:

•No elevation in urine osmolality in complete nephrogenic DI.

•A small (up to 45 percent) elevation in urine osmolality in partial nephrogenic

DI.

Although the directional change in partial nephrogenic DI is similar to that

seen with partial central DI, the absolute numbers are quite different. Patients
with the central DI usually achieve a urine osmolality of 300 mosmol/kg or
higher after desmopressin, while patients with symptomatic acquired
nephrogenic DI typically have a persistently dilute urine that rises, but
remains well below isosmotic, after desmopressin [10,11]. The history may
also be helpful in distinguishing between these disorders.

●Primary polydipsia will be associated with a rise in urine osmolality, usually to

above 500 mosmol/kg, and no response to desmopressin, since endogenous
release is intact. Maximum concentrating ability is frequently impaired in this
disorder, resulting in a maximum urine osmolality that may reach 500 to 600
mosmol/kg, as compared with 800 mosmol/kg or more in normal subjects. This
acquired defect appears to be due to two effects of chronic polydipsia and
polyuria: partial wash out the medullary interstitial gradient and downregulation
of ADH release [13].

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A properly performed test in which ADH is not given until the plasma osmolality
exceeds 295 mosmol/kg will usually establish the correct diagnosis. If the diagnosis
remains uncertain, it is reasonable to try desmopressin therapy. The polyuria and
polydipsia will rapidly reverse with central DI. (See "Treatment of central diabetes
insipidus".)

However, careful monitoring is essential; the urine output will also fall in primary
polydipsia, but the combination of persistent polydipsia and a concentrated urine can
lead to potentially severe symptomatic hyponatremia.

Sources of error — There are two major potential errors with the water restriction test.
First, patients with partial central DI may be hyperresponsive to the submaximal rise in
ADH induced by water restriction, perhaps due to receptor upregulation. As a result,
they may be polyuric at the normal plasma osmolality of 285 to 290 mosmol/kg when
ADH levels are very low but have a maximally concentrated urine at a plasma
osmolality above 295 mosmol/kg when ADH levels are somewhat higher. In this
setting, desmopressin will be without effect, resulting in a pattern suggestive of primary
polydipsia [11]. As noted above, the history may provide important clues in this setting,
with abrupt onset favoring central DI and gradual onset, particularly with a history of
psychiatric illness, favoring primary polydipsia.

Second, polyuria developing during pregnancy may result from the release of
vasopressinases from the placenta (a disorder that has been called gestational DI). In
this setting, the patient will be resistant to aqueous vasopressin (mistakenly suggesting
nephrogenic DI) but will respond to desmopressin, which is resistant to vasopressinase
[14]. (See "Maternal adaptations to pregnancy: Renal and urinary tract physiology".)

Plasma and urine ADH measurement — Unless the history and water restriction test
provide unequivocal results, plasma or urine samples collected at baseline and
following water deprivation (prior to the administration of antidiuretic hormone [ADH])
should be sent for measurement of ADH [11,15]:

●If there is an increase in plasma or urine ADH in response to the rising plasma
osmolality, central DI is excluded.

●If there is an appropriate elevation in urine osmolality as ADH secretion is

increased, nephrogenic DI is excluded.

However, measurement of ADH concentrations may be misleading for several reasons

[16]:

●The commercially available assays for both plasma and urine ADH are not very
sensitive, especially in the range below 3 pg/mL.

●ADH in the circulation is largely bound to platelets, and, without special handling
of the specimen, falsely high and falsely low levels can be seen.

●ADH is unstable in isolated plasma, even when stored at -20ºC so that send-out
assays may be unreliable. Even highly sensitive assays may be misleading in

9
 patients with primary polydipsia since chronic overhydration can cause partial
suppression of ADH release, mimicking the pattern in central DI [13].

Urinary assays have been suggested since the ADH concentration is higher in urine
and the plasma separation issues may not apply. However, there are few data to
support this approach.

Alternatively, copeptin (the C-terminal glycoprotein moiety of pro-AVP) can be

measured. Copeptin measurements seem to be promising and less complicated than
ADH determinations [12,17], although they are not widely available.

SOLUTE DIURESIS — The above discussion has emphasized the diagnostic

approach to a water diuresis. However, in some patients with polyuria, particularly of
acute onset, the increase in urine output is due to a solute or osmotic diuresis in which
the primary abnormality is an inability to reabsorb a substantial proportion of the filtered
solute.

The major causes of polyuria due to a solute (osmotic) diuresis are as follows:

●Glucose diureses – Glucosuria, usually due to uncontrolled diabetes mellitus, is

the major cause of an osmotic diuresis in outpatients. In addition, inpatients with
severe central DI who are treated with large volumes of intravenous dextrose and
water can develop hyperglycemia, glycosuria, and polyuria that is antidiuretic
hormone (ADH) resistant. (See "Treatment of central diabetes insipidus".)

●Urea diuresis – Polyuria due to a urea diuresis (in which urea acts as an osmotic
agent) may develop in several settings. Large amounts of urea that induce this
diuresis may be derived from:

•Resolution from azotemia.

•Administration of urea as therapy in patients with hyponatremia. (See

"Treatment of hyponatremia: Syndrome of inappropriate antidiuretic
hormone secretion (SIADH) and reset osmostat", section on 'Urea'.)

•Tissue catabolism. Lean body tissues are approximately 20 percent protein

by weight, and protein catabolism results in the production of urea.

•Administration of high amounts of protein orally or intravenously, which will

be catabolized to urea.

●Sodium diuresis – Volume expansion due, for example, to large volumes of

intravenous saline or to the release of bilateral urinary tract obstruction may
produce a sodium diuresis and polyuria [1,18-20].

A solute diuresis can be differentiated from DI based upon the following findings:

●The urine osmolality in a solute diuresis is usually above 300 mosmol/kg, in

contrast to the dilute urine typically found with a water diuresis.

10
 ●Total solute excretion (calculated on a 24-hour urine collection from the product
of the urine osmolality and the urine volume [in liters]) is normal with a water
diuresis (600 to 900 mosmol per day on a typical Western diet) but markedly
increased with an osmotic diuresis. (See "Patient education: Collection of a
24hour urine specimen (Beyond the Basics)".)

Salt-wasting nephropathy: Not usually a cause of polyuria — As a general rule,

underlying renal disease can impair sodium conservation in the presence of volume
depletion. However, except in rare cases of Bartter syndrome [21], salt-wasting
nephropathies do not cause true polyuria. This is in part due to the phenomenon of
tubuloglomerular feedback in which increased sodium chloride delivery to the macula
densa (due to decreased reabsorption in the more proximal segments) results in
afferent arteriolar constriction and a fall in glomerular filtration rate, thereby limiting the
degree of sodium chloride loss (figure 2) [22,23]. (See "Bartter and Gitelman
syndromes", section on 'Bartter syndrome'.)

Thus, polyuria in which there is a marked increase in sodium excretion (ie, sodium salts
make up most of the increased solute excretion) is almost always appropriate,
resulting from volume expansion induced either by saline loading or, following relief of
urinary obstruction, by fluid retained during the period of obstruction [19,20]. In addition
to the excretion of retained sodium, increased urea excretion can contribute to a
postobstructive diuresis when urea has also been retained as evidenced by a
substantial increase in blood urea nitrogen. (See "Clinical manifestations and diagnosis
of urinary tract obstruction and hydronephrosis", section on 'Prognosis and recovery of
renal function'.)

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Many clinicians faced with a urine output that may initially exceed 1000 mL per hour in
adults feel compelled to replace the urine output with intravenous fluids. This will only
prolong the polyuria driven by increased sodium excretion since volume expansion will
persist. Optimal therapy of a postobstructive diuresis consists of fluid infusion at a
maintenance level, such as 75 mL of one-half isotonic saline per hour. The
development of volume depletion, as evidenced by hypotension or a rise in the blood
urea nitrogen, is unusual with this regimen [19,20].

An exception to this general rule can occur in infants with congenital obstructive
uropathy in whom the associated ADH resistance is sufficiently severe that the
maximum urine osmolality is well below that of the plasma. In these infants, relief of the
obstruction can lead to a marked water diuresis with subsequent hypernatremia
[24,25]. Following relief of obstruction, fluid status should be carefully monitored and
fluid therapy adjusted as necessary.

It is possible that some of these patients have congenital nephrogenic DI, with polyuria,
not obstruction, being responsible for urinary tract and bladder dilation [26-28]. (See
"Treatment of nephrogenic diabetes insipidus".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored

guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Fluid and electrolyte disorders".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education

materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces
are written in plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on "patient info" and the keyword(s) of
interest.)

●Basics topics (see "Patient education: Diabetes insipidus (The Basics)")

SUMMARY AND RECOMMENDATIONS

Overview — Polyuria has generally been defined as a urine output exceeding 3

L/day in adults and 2 L/m2 in children. There are three major causes of polyuria
associated with the excretion of large volumes of dilute urine (urine osmolality usually
below 250 mosmol/kg), each of which has several underlying etiologies (see
'Causes' above):

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 ●Primary polydipsia (also called psychogenic polydipsia), characterized by a
primary increase in water intake (see "Causes of hyponatremia in adults", section
on 'Primary polydipsia')

●Central diabetes insipidus (DI), due to deficient secretion of antidiuretic hormone

(ADH) (see "Clinical manifestations and causes of central diabetes insipidus")

●Nephrogenic DI, characterized by normal ADH secretion but varying degrees of

renal resistance to its water-retaining effect (see "Clinical manifestations and
causes of nephrogenic diabetes insipidus")

Differential diagnosis — Other conditions that may result in the complaint of polyuria
include nocturia due to prostatic hypertrophy and a solute (osmotic) diuresis due, for
example, to hyperglycemia or relief of urinary tract obstruction. As a general rule,
saltwasting nephropathies do not cause sufficient sodium wasting to induce true
polyuria. A solute diuresis can be differentiated from DI based upon the following:

●The urine osmolality in a solute diuresis is usually above 300 mosmol/kg, in

contrast to the dilute urine in a water diuresis.

●Total solute excretion is normal with a water diuresis (600 to 900

mosmol/day) but markedly increased with an osmotic diuresis.

Diagnosis — The cause of polyuria (water diuresis) is often suggested from the history
(eg, age of onset, rate of onset, eliciting the possible presence of the different causes
of DI, family history) and by the plasma sodium concentration. (See 'Onset of polyuria'
above and 'Family history' above.)

Even if the history and/or plasma sodium concentration and urine osmolality appear to
be helpful, we recommend confirming the diagnosis in most patients by examining the
response (urine volume and osmolality) to water restriction and, if appropriate,
administration of exogenous ADH once the plasma osmolality reaches 295 to
300 mosmol/kg or the plasma sodium is 145 mEq/L or higher. We prefer
desmopressin to aqueous vasopressin. (See 'Plasma sodium and urine
osmolality'above and 'Water restriction test' above.)

We recommend obtaining blood at baseline and after water restriction, to be sent for
plasma ADH levels if the response to the water restriction test is equivocal. Urine ADH
testing may be performed if high sensitivity plasma ADH assays are not available. (See
'Plasma and urine ADH measurement' above.)

We recommend not performing a water restriction test in patients with a dilute urine
who are strongly suspected of having nephrogenic DI (eg, newborns and very young
infants and long-term lithium use in adults). In these settings, testing for a lack of
response to desmopressin can be performed without prior water restriction. (See
'Infants and children' above.)

The response to water restriction and desmopressin helps establish the diagnosis (see
'Interpretation' above):

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 ●A submaximal increase in urine osmolality in response to water deprivation (but
usually to ≥300 mosmol/kg), with desmopressin resulting in a rise in urine
osmolality of more than 100 percent in complete central DI and 15 to 50 percent in
partial central DI.

●Submaximal rise in urine osmolality in response to water restriction (but to well

below 300 mosmol/kg), with desmopressin producing little or no elevation in urine
osmolality in complete nephrogenic DI, and a small (<45 percent) elevation in
urine osmolality with partial nephrogenic DI.

●Primary polydipsia will be associated with a rise in urine osmolality, usually to

above 500 mosmol/kg, and no response to desmopressin since endogenous
release is intact.

If the history and water restriction test provide equivocal results, plasma samples
collected at baseline and following water deprivation (prior to the administration of
ADH) should be sent for measurement of ADH (see 'Plasma and urine ADH
measurement' above):

●Nephrogenic DI is excluded if there is an appropriate relationship between the

rise in urine osmolality and plasma ADH.

●Central DI is excluded if there is an appropriate rise in plasma ADH with the rise
in plasma sodium or osmolality.

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