COASS NEURO RSAL PERIODE 20 JUNE - 30JULY

2016

Diabetes insipidus
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What is Diabetes Insipidus?

Diabetes Insipidusis a disease characterised by the
passage
of
large
volumes(>3L/24hrs)of
dilute
urine(osmolality
<300
mOsmol/Kg).
It
affects
approximately 3 in 100,000 people.In some cases the
volume of urine produced can be as much as 20 litres in a
24 hour period and therefore rapid dehydration can easily
occur, leading to death if not managed appropriately.
Diabetes Insipidus has a number of causes and therefore
use of the correct investigations is essential to reach a
definitive diagnosis.

Pathophysiology
1.Vasopressin(Anti-Diuretic Hormone)is produced by
the hypothalamus in response to increased serum
osmolality
2.Vasopressin is then transported to the posterior
pituitary gland
3.It is then released into the circulatory system via
the posterior pituitary gland
4.It then travels to the kidneys where it binds to
vasopressin receptors on the distal convoluted
tubules
5.Thiscauses Aquaporin-2 channels to move from the
cytoplasm into the apical membrane of the tubules.

These aquaporin-2 channels allow water to be reabsorbed out of

the collecting ducts & back into the blood stream.
This results in both a decrease in volume & an increase in
osmolality (concentration) of the urine been excreted

6.The extra water that has been reabsorbed re-enters

the circulatory system, reducing the serum osmolality
7.This reduction in serum osmolality is detected by
the hypothalamus & results in decreased production
of vasopressin.

Causes
Neurogenic
Diabetes insipidus can occur as a result of decreased circulating levels of Vasopressin(ADH). Vasopressin is
responsible for instructing the kidneys to retain fluid. Therefore decreased circulating levels of ADH results in
the production of copious volumes of urine. Because vasopressin is produced by the hypothalamus &
released by the posterior pituitary gland, pathology impacting either of these glands has the potential to
cause diabetesinsipidus.
Acquired

Familial
Mutations in the
Vasopressin
gene(e.g. Autosomal
dominant AVP-NPII)
Results in inadequate
production of functional
Vasopressin

Tumours Pituitary adenomas(20%), Craniopharyngiomas, Metastases

Trauma 17% of casese.g. Head injury
Neurosurgery 9% of cases
Infections meningitis
Vascular Sheehans syndrome
Complication of pregnancy in which the pituitary blood supply is causing
necrosis of the gland
Sarcoidosis formation of granulomas in pituitary
Haemochromotosis deposition of iron in pituitary/hypothalamic tissue
causing damage
Langerhans cell histiocytosis
Proliferation ofLangerhanscells which form lesions in many organs
including
pituitary stalk
Idiopathic 25% of cases.

Causes

Nephrogenic
The kidneys are responsible for reabsorbing fluid
when ADH binds to their receptors. Anything which
interferes with this binding or damages the kidneys
has
the potential to cause diabetesinsipidus.
Familial
Acquired

X-linked recessive mutations

in the ADH receptor gene
Autosomal recessive
aquaporin-2 gene aquaporin 2
isresponsible for the
reabsorption of water from
urine4

Metabolic hypercalcaemia, hyperglycaemia,

hypokalaemia
Drugs lithium, demeclocycline both
interfere with the binding of ADH
Chronic renal disease polycystic kidneys
Amyloidosis
Post obstructive uropathy

Causes
Dipsogenic

Dipsogenic diabetes insipidus is caused by a defect or damage to the hypothalamus causing

malfunction of the thirst mechanism. As a result the individual is excessively thirsty regardless
of their fluid status. The individual therefore consumes large volumes of fluid which suppresses
secretion of vasopressin and increases urine output. It is dangerous to give a vasopressin
analogue such as Desmopressin in these circumstances as the individual will continue to feel
thirsty and consume large volumes of fluids which could result in fluid overload.
Gestational

Gestational diabetes insipidus only occurs during pregnancy. During pregnancy the placenta
produces vasopressinase which breaks down vasopressin. Gestational diabetes insipidus is
therefore thought to be caused by overproduction of vasopressinase by the placenta causing a
lack of functional vasopressin.

Primary Polydipsia

Primary polydipsia is characterised by an individual consuming large volumes of fluids and as a

result producing large volumes of dilute urine. The symptoms of primary polydipsia are therefore
very similar to those of diabetes insipidus however a fluid deprivation test can help distinguish
the diseases. Most often primary polydipsia is due to a psychological disorder.

Symptoms & Signs

Symptoms
Excessive
urination(>3L/24hrs)
Excessive thirst(especially
for ice cold water)
Nocturia
Dehydration
headache,dizziness,
fainting, dry mouth

Signs
Hypotension
Dilute urine
Reduced capillary refill
time

Investigations
Measure urine output confirm more than 3000ml a day
Exclude diabetes mellitus dipstick urine for glucose & assess blood glucose level
Exclude renal failure
Check electrolyte levels
Hypokalaemia & Hypercalcaemia nephrogenic DI
Hypernatraemia can develop due to dehydration
Fluid deprivation test
Helps determine cause of DI neurogenic, nephrogenic, primary polydipsia
Patient is allowed fluids overnight
Patient is then deprived of fluids for 8 hours(or until loss of 5% of body weight if earlier)
The patient is weighed hourly
Plasma osmolality is measured every 4 hours
Urine volume & Osmolality is measured every 2 hours
At the end of the deprivation period the patient is given 2mcg of IM Desmopressin
Urine volume & Serum osmolality are then measured over the next 4 hours
MRI scan head looking for tumours pituitary adenomas, craniopharyngomas

Diagnosis
The fluid deprivation test is the most useful in diagnosing diabetesinsipidus
It can confirm the presence of DI and suggest which type of DI the individual
likely has
If the serum osmolality is >305mOsm/kg at any point the patient has DI(stop
test)

Diagnosis
Neurogenic
If the diagnosis is Neurogenic DI the urine osmolality will be low after fluid deprivation but
normalise after desmopressin is given. This is because neurogenic DI is caused by the lack of
vasopressin production therefore giving a synthetic form of vasopressin such as desmopressin
normalises levels of the hormone resulting in the normalisation of serum & urine osmolality.
Nephrogenic
If the diagnosis is Nephrogenic DI then the urine osmolality will remain low throughout regardless
of desmopressin. This is because the kidneys have a problem which prevents them from been
able to respond to vasopressin, therefore giving extra synthetic vasopressin will have no effect.
Primary Polydipsia
If the diagnosis is Primary Polydipsia the urine osmolality will remain high after fluid deprivation
as well as after desmopressin is given. This is because the patients vasopressin axis is intact
and otherwise completely normal.
Partial DI or Polydipsia
If the diagnosis is that of Partial DI or Polydipsia the picture may be mixed. The patient may have
aslightlylow osmolality after fluid deprivation and may not reach normal urine osmolality after
desmopressin. This kind of picture would require more thorough investigation to determine a

Management
Neurogenic
Give Desmopressin

Vasopressin analogue
Binds to v2 receptors on kidney allowing water to be reabsorbed
Drug can be given orally, intranasally, parenterally or bucally
Dose varies significantly between patients
Osmolality & Serum Sodium need monitoring can cause hyponatraemia or hypo-osmolality

Chlorpropamide & Carbamazepine can be used to increase activity of vasopressin

Nephrogenic
Advise patient to maintain adequate fluid intake
Correct any metabolicderangementshypercalcaemia, hyperglycaemia,
hypokalaemia
Stop any drugs that may be to blamelithium, demeclocycline both interfere with
the binding of ADH
High dose Desmopressin up to 5mcg IM
Thiazide diuretics / Prostaglandin Synthase Inhibitors reduce action of
prostaglandins which can inhibit vasopressins action on the kidney

Management
Partial Diabetes Insipidus
Advise patient to maintain adequate fluid intakeusually
nodrugs required
Thirst mechanism must be normal
Polyuria must be mild (<4L/24hrs)
Primary Polydipsia
Often very difficult to manage
The underlying psychiatric disorder needs to be treated

Reference
From http://geekymedics.com/diabetes-insipidus/
1.Oxford handbook of Endocrinology & Diabetes
2.Saborio, P.; Tipton, G. A.; Chan, J. C. M. (2000). Diabetes
Insipidus.Pediatrics in Review21(4): 122129
3.Makras P, Papadogias D, Kontogeorgos G, Piaditis G, Kaltsas G
(2005). Spontaneous gonadotrophin deficiency recovery in an
adult patient with Langerhans cell histiocytosis
(LCH).Pituitary8(2): 16974
4.Wildin, Robert (2006).What is NDI?. The Diabetes Inspidus
Foundation