The fluid deprivation test is an important diagnostic tool used to distinguish between central diabetes insipidus and other causes of polyuria such as primary polydipsia. It involves withholding fluids from a patient for a period of time while closely monitoring urine output, osmolality, and electrolyte levels to check for an appropriate response to ADH.

1. ‫الجديد‬ ‫العام‬ ‫المنصوره‬ ‫مستشفى‬(‫الدولى‬)

2. Diabetes insipidus

3. How is fluid regulated in the
body?
 body regulates fluid by balancing liquid intake and
removing extra fluid.
 Thirst usually controls a person’s rate of liquid intake
 urination removes most fluid
 sweating, breathing, or diarrhea.
 The hormone vasopressin, also called antidiuretic
hormone, controls the fluid removal rate through
urination.

4. ADH
 augment the water permeability of the luminal
membranes of the cortical and medullary collecting
tubules,
 promotes water reabsorption via osmotic
equilibration with the hypertonic interstitium.
 promotes urinary concentration is available
elsewhere.

5.  Patients with moderate to severe nephrogenic or
central DI typically present with polyuria, nocturia,
and polydipsia.
 Polyuria is arbitrarily defined as a urine output
exceeding 3 L/day in adults or 2 L/m2 in children.

6. Causes of polyuria other than DI
 include primary polydipsia and increased solute excretion
due to one or more of the following: glucosuria in
uncontrolled diabetes mellitus, urea with a high protein
diet, or sodium chloride and urea in a postobstructive
diuresis.
 In addition, glucosuria can contribute to polyuria in
patients with severe DI when hyperglycemia is induced by
the administration of large volumes of intravenous
dextrose in water

7. polyuria
 Renal diseases such as bilateral urinary tract obstruction,
sickle cell disease or trait, renal amyloidosis, and
Sjögren's syndrome.
 Use of cidofovir , foscarnet , vasopressin V2 receptor
antagonists, amphotericin B , demeclocycline ,
ifosfamide , ofloxacin , orlistat , and didanosine .
 Pregnancy, which is associated with release of a
vasopressinase from the placenta.
 Craniopharyngioma surgery. Bardet-Biedl syndrome,
Bartter syndrome, nephronophthisis, cystinosis, familial
hypomagnesemia with hypercalciuria and
nephrocalcinosis (FHHNC), and the syndrome of apparent
mineralocorticoid excess

8.  Hypercalcemia may also impair water reabsorption
by decreasing the number of water channels in the
collecting tubules.
 Hypokalemia — Persistent severe hypokalemia
(plasma potassium concentration usually below 3
meq/L) can impair urinary concentrating ability. As
with hypercalcemia, both decreased collecting tubule
responsiveness to ADH (which may be mediated by
decreased expression of aquaporin-2) and diminished
sodium chloride reabsorption in the thick ascending
limb have been demonstrated in experimental animals

9.  There are two major receptors for ADH: the V1 and V2
receptors. Activation of the V1 receptors induces
vasoconstriction and enhancement of prostaglandin release
while the V2 receptors mediate the antidiuretic response as
well as other functions A third receptor, the V3 or V1b
receptor, appears to mediate the effect of ADH on the pituitary,
facilitating the release of ACTH

10. ADH
 The principal ADH-sensitive water channel, called
aquaporin-2 , under the influence of ADH, allowing
water to be reabsorbed down the favorable osmotic
gradient
 A defect in any step in this pathway, such as
attachment of ADH to its receptor or the function of the
water channel, can cause resistance to the action of
ADH and an increase in urine output. This disorder is
called nephrogenic diabetes insipidus

11. Factors regulating the release of ADH
Stimuli
Hyperosmoity
Hypovolemia Stress (eg, pain) Nausea Pregnancy
Hypoglycemia Nicotine Morphine
Inhibitors
Hypoosmolality Hypervolemia Ethanol Phenytoin

13. Synonyms of Central Diabetes Insipidus
 CDI
 neurogenic diabetes insipidus
 neurohypophyseal diabetes insipidus
 vasopressin-sensitive diabetes insipidus

14. Synonyms of Nephrogenic Diabetes
Insipidus
 acquired nephrogenic diabetes insipidus
 congenital nephrogenic diabetes insipidus
 hereditary nephrogenic diabetes insipidus
 NDI
 vasopressin-resistant diabetes insipidus

15. What are the types of diabetes insipidus?
 central
 nephrogenic
 dipsogenic
 gestational

16. What are the complications of diabetes
insipidus?
 The main complication of diabetes insipidus is dehydration if fluid
loss is greater than liquid intake. Signs of dehydration include
 thirst
 dry skin
 fatigue
 sluggishness
 dizziness
 confusion
 nausea
 Severe dehydration can lead to seizures, permanent brain damage, and even
death

17. How is diabetes insipidus diagnosed?
 medical and family history
 physical exam
 urinalysis
 blood tests
 magnetic resonance imaging (MRI

18. NDI
most cases of hereditary NDI are inherited
as X-linked recessive disorders.
Rare cases are inherited as an autosomal recessive or dominant disorder.
Two different genes have been identified that cause hereditary NDI.
NDI may also be acquired during life as a result of drug use (e.g., lithium
therapy), kidney disease, obstruction of the tubes that carry urine from
the kidneys to the bladder (ureters), and prolonged metabolic
imbalances such as low levels of potassium in the blood (hypokalemia) or
high levels of calcium in the blood (hypercalcemia).
NDI may also be a temporary complication associated with pregnancy.

19. NDI
 Infants with NDI may experience repeated episodes of
dehydration, which can result in weakness, confusion,
dry mucous membranes, dry skin, and weight loss.
 If left untreated, severe dehydration may develop.
Repeated episodes of severe dehydration may result in
significant abnormalities including seizures, brain
damage, developmental delays, and physical and
mental disability

20. NDI
 Because of the chronic excretion of large amounts of
urine, additional symptoms may develop as affected
individuals age including bedwetting at night
(nocturnal enuresis), abnormal accumulation of urine
in the kidneys (hydronephrosis), swelling (distention)
of the ureters with urine due to blockage
(hydroureter), and an abnormally large bladder
(megacystis). Some individuals develop widening
(dilatation) of the urinary tract

21. NDI
 Adults with NDI may also develop orthostatic
hypotension, a condition in which there is a dramatic
decrease in blood pressure upon standing or sitting.
Orthostatic hypotension can result in dizziness or
momentary loss of consciousness (syncope)

22. NDI
 X-linked recessive genetic disorders are conditions caused by an abnormal gene on
the X chromosome. Females have two X chromosomes but one of the X chromosomes
is “turned off” and all of the genes on that chromosome are inactivated. Females who
have a disease gene present on one of their X chromosomes are carriers for that
disorder. Carrier females usually do not display symptoms of the disorder because it is
usually the X chromosome with the abnormal gene that is “turned off”. A male has one
X chromosome and if he inherits an X chromosome that contains a disease gene, he
will develop the disease. Males with X-linked disorders pass the disease gene to all of
their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons
because males always pass their Y chromosome instead of their X chromosome to male
offspring. Female carriers of an X-linked disorder have a 25% chance with each
pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-
carrier daughter, a 25% chance to have a son affected with the disease, and a 25%
chance to have an unaffected son.

23. NDI
 Investigators have determined that X-linked recessive
cases of NDI are caused by disruptions or changes
(mutations) of the AVPR2 gene located on the on the
long arm (q) of the X chromosome (Xq28).
 Investigators have determined that most (but not all)
patients of autosomal recessive and dominant NDI are
caused by mutations of the aquaporin-2 (AQP2) gene
located on the long arm (q) of chromosome 12 (12q13).

24. Central diabetes insipidus (CDI)
causes
idiopathic disease, familial and congenital disorders,
neurosurgery or trauma, primary or secondary cancers,
hypoxic encephalopathy, infiltrative disorders, post-
supraventricular tachycardia, and anorexia nervosa. The
vast majority of cases are due to idiopathic CDI or
result from primary or secondary tumors, or infiltrative
diseases (such as Langerhans cell histiocytosis

25.  lesion that also impairs thirst, thereby causing hypodipsia
or adipsia; in this setting, the plasma sodium concentration
can exceed 160 meq/L Adipsic DI is associated with
significant morbidity including obesity, sleep apnea, venous
thrombosis during episodes of hypernatremia,
thermoregulatory dysfunction, seizures, and significant
mortality
 In addition, 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.

26. Case Report
Transient Central Diabetes
Insipidus and Marked
Hypernatremia following
CardiorespiratoryArrest
 Case Reports in Nephrology
Volume 2017, Article ID 1574625,
3 pages
https://doi.org/10.1155/2017/157462
5

27. Primary central diabetes
insipidus
 lesion noted on MRI of the pituitary and
hypothalamus)
 about one-third of all cases
 may also be genetic. Familial
 diabetes insipidus occurs as a dominant genetic trait
 with symptoms developing at about 2 years of age.

28. DIDMOAD
 Diabetes insipidus also occurs in Wolfram syndrome, a
rare autosomal recessive disorder that is also known by the
acronym DIDMOAD (diabetes insipidus, type 1 diabetes
mellitus, optic atrophy, and deafness). Although DIDMOAD
 manifestations usually present in childhood, they
may not occur until adulthood, along with depression
and cognitive problems

29. Secondary central diabetes
insipidus
 due to damage to the hypothalamus or pituitary stalk
by tumor, hypophysitis,infarction, hemorrhage,
 anoxic encephalopathy, surgical or accidental trauma,
 infection (eg, encephalitis, tuberculosis, syphilis), or
granulomas (sarcoidosis or Langerhans cell
granulomatosis).
 Metastases to the pituitary are more likely to cause
diabetes insipidus (33%) than are pituitary adenomas
(1%). Central diabetes insipidus can also be idiopathic.

30. Vasopressinase-induced
diabetes insipidus
 seen in the last trimester of pregnancy, associated with
oligohydramnios,preeclampsia, or hepatic dysfunction,
and in the puerperium. A circulating enzyme destroys
native vasopressin; however, synthetic desmopressin is
unaffected

31. The treatment of choice for transient diabetes insipidus
of pregnancy is?
A-AVP(Atrialvasopressin)
B- Desmopressin
C-Tolvaptan
D-Demeclocycline
E-none of the above

32.  Option B is the correct answer.
 Transient diabetes insipidus of pregnancy is caused by increased
expression of vasopressin from the placenta. This results in a
greater breakdown of vasopressin. Desmopressin (DDAVP),
however, is not a substrate for this enzyme and remains effective.
 Tolvaptan is a vasopressin antagonist and will act as an
aquaretic, thus exacerbating diabetes insipidus.
It is a category C drug for use in pregnancy.
 Demeclocycline inhibits adenylatecyclase activity, which is
downstream of AVP binding to the V2 receptor and has been
described as correcting Hyponatraemia in SIADH.
However, it is potentially nephrotoxic with variable efficacy.
It is a category D drug in pregnancy due to its effect on skeletal
formation, and should not be used.

33. Urinalysis
 patient collect urine in a special container over a 24-
hour period to measure the total amount of urine
produced by the kidneys
 a 24-hour urine collection for volume and creatinine.
A urine volume of less than 2 L/24 h (in the absence of
hypernatremia) rules out diabetes insipidus.
 .

34. Blood Tests
 measures sodium levels, which can help diagnose
diabetes insipidus
 Hyperuricemia occurs in many patients with diabetes insipidus,
since reduced vasopressin stimulation of the renal V1
receptor causes a reduction in the renal tubular clearance
of urate

35. 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
 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

36. Fluid Deprivation Test
 A short form of the deprivation test. A health care
provider instructs the patient to stop drinking all
liquids for a specific period of time, usually during
dinner. The next morning, the patient will collect a
urine sample at home.

37. A formal fluid deprivation test.
 A health care provider performs this test in a hospital to continuously monitor the
patient for signs of dehydration. Patients do not need anesthesia. A health care
provider weighs the patient and analyzes a urine sample. The health care provider
repeats the tests and measures the patient's blood pressure every 1 to 2 hours until
one of the following happens:
o The patient's blood pressure drops too low or the patient has a rapid heartbeat when standing.
o The patient loses 5 percent or more of his or her initial body weight.
o Urine concentration increases only slightly in two to three consecutive measurements.
 At the end of the test, a health care provider will compare the patient's blood
sodium, vasopressin levels, and urine concentration to determine whether the
patient has diabetes insipidus. Sometimes, the health care provider may administer
medications during the

38. 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.

39. 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

40. vasopressin challenge test”
Desmopressin acetate 0.05–0.1 mL (5–10 mcg) intranasally
(or 1 mcg subcutaneously or intravenously) is given,
 measurement of urine volume for 12 hours before and
12 hours after administration. Patients with central diabetes
insipidus notice a distinct reduction in thirst and polyuria;
serum sodium usually remains normal.
The dosage of desmopressin is doubled if the response is
marginal. If symptoms of hyponatremia develop, serum
sodium must be assayed immediately

41. MRI
 nonfamilial central diabetes insipidus, MRI of the
pituitary and hypothalamus is done to look for mass
lesions. If the pituitary stalk is thickened, the cause may be
Langerhans cell histiocytosis, sarcoidosis, or lymphocytic
hypophysitis.
With central diabetes insipidus, MRI T-1-weighted imaging
shows an absence of the usual hyperintensesignal (bright
spot) in the posterior pituitary

42. Treatment
 Mild cases of diabetes insipidus require no treatment
other than adequate fluid intake.
 Reduction of aggravating factors (eg, corticosteroids)
will improve polyuria

43.  Desmopressin acetate is the treatment of choice for
central diabetes insipidus.
It is also useful in vasopressinase-induced
diabetes insipidus associated with pregnancy or
the puerperium, since desmopressin acetate is resistant
to degradation by the circulating vasopressinase

44.  Desmopressin acetate (100 mcg/mL solution) is given
intranasally every 12–24 hours as needed for thirst and
polyuria. It may be administered via metered-dose nasal
inhaler containing 0.1 mL (10 mcg/spray) or via a calibrated
rhinal tube. The starting dose is one metered-dose
spray or 0.05–0.1 mL every 12–24 hours, and the dose is
then individualized according to response. Nasal
desmopressin may cause rhinitis or conjunctivitis.

45.  Oral desmopressin is also available as 0.1 mg and 0.2 mg
tablets and is given in a starting dose of 0.05 mg twice daily and
increased to a maximum of 0.4 mg every 8 hours
. Oral desmopressin is particularlyuseful for patients in whom
rhinitis or conjunctivitis develops from the nasal preparation.
Gastrointestinal symptoms,asthenia, and mild increases in hepatic
enzymes can occur with the oral preparation.
 Desmopressin can also be given intravenously, intramuscularly,
or subcutaneously in doses of 1–4 mcg every12–24 hours as
needed.

46.  Desmopressin may cause hyponatremia, but this is
uncommon if minimum effective doses are used and the
patient allows thirst to occur periodically.
Desmopressin can sometimes cause agitation,
emotional changes, and depression with an increased
risk of suicide

47. 46-year-old woman is admitted for polyuria, polydipsia, and nocturia. She fulfills her
thirst mostly with ice water. Her serum [Na+] is 158 mEq/L with urine osmolality of 98
mOsm/kg H2O. Which one of the urine osmolalities (mOsm/kg H2O) is consistent with
her diagnosis?
Osmolality before dehydration after 12 h dehydration after vasopressin
A 600 1100 1080 NORMAL
B 100 120 360 CDI
C 180 350 500 Partial CDI
D 300 310 314 NDI
E 120 500 520 PSYCHOGENIC
Based on the history and urine osmolality, the patient has central diabetes insipidus
(CDI). Option B is consistent with CDI.
Options A, C, D, and E are consistent with normal subject, partial CDI, nephrogenic DI,
and psychogenic polydipsia, respectively

48. THANK YOU