Diabetes Insipidus

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Diabetes insipidus\: characterised by the passage of large volumes (>3L/24hrs) of dilute urine (osmolality \<300
mOsmol/Kg).
Normal physiology\: ADH (vasopressin) from the hypothalamus, stored in the posterior pituitary, binds to kidney receptors to
reabsorb water, reducing urine volume and increasing osmolality.
Neurogenic DI\: caused by decreased ADH; causes include mutations, idiopathic, tumours, trauma, infections, vascular
issues, sarcoidosis, haemochromatosis.
Nephrogenic DI\: kidneys fail to respond to ADH; causes include genetic mutations, metabolic disturbances, drugs (lithium,
demeclocycline), chronic renal disease, amyloidosis, obstructive uropathy.
Dipsogenic DI\: hypothalamic disease or trauma a
secretion.
Gestational DI\: overproduction of vasopressinase by the placenta during pregnancy, leading to functional vasopressin
de
test.
Primary polydipsia\: excessive
Symptoms\: excessive urination (>3L/24hrs), excessive thirst (especially for ice-cold water), nocturia, dehydration symptoms
(headache, dizziness, dry mouth).
Signs\: hypotension, dilute urine, dehydration signs (dry mucous membranes, prolonged capillary re
Investigations\: 24-hour urine collection, plasma glucose, U&Es, urine speci
deprivation test, MRI brain, renal tract ultrasound.
Diagnosis\:
Neurogenic DI\: low urine osmolality normalises with desmopressin.
Nephrogenic DI\: low urine osmolality regardless of desmopressin.
Primary polydipsia\: high urine osmolality).
Management\:
Neurogenic DI\: desmopressin (oral, intranasal, parenteral), regular monitoring of serum sodium osmolality.
Nephrogenic DI\: access to water, correct metabolic abnormalities, stop causative medications, high-dose desmopressin for
mild-to-moderate cases.
Primary polydipsia\: treat underlying psychiatric disorder.
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A comprehensive topic overview

What is diabetes insipidus?

Diabetes insipidus (DI) is a disease characterised by the passage of large volumes (>3L/24hrs) of dilute urine (osmolality
\<300 mOsmol/Kg).
¹
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.Normal physiology
1. Vasopressin (antidiuretic hormone/ADH) is produced by the hypothalamus in response to increased serum osmolality.
2. Vasopressin is then transported to the posterior pituitary gland, where it is released into the blood.
3. Vasopressin then travels to the kidneys where it binds to vasopressin receptors on the distal convoluted tubules.
4. This binding causes aquaporin-2 channels to move from the cytoplasm into the apical membrane of the tubules\:
Aquaporin-2 channels allow water to be reabsorbed out of the collecting ducts and back into the bloodstream
This results in both a decrease in volume and an increase in osmolality (concentration) of the urine being excreted
5. The extra water that has been reabsorbed re-enters the circulatory system, reducing serum osmolality.
6. This reduction in serum osmolality is detected by the hypothalamus as negative feedback, resulting in decreased
production of vasopressin.
An illustration of how serum osmolality is regulated in healthy individuals.

Causes of diabetes insipidus

Neurogenic diabetes insipidus¹
Neurogenic diabetes insipidus occurs as a result of decreased circulating levels of vasopressin (ADH). Vasopressin is
responsible for promoting the kidneys to retain
production of increased volumes of urine. Vasopressin is produced by the hypothalamus and released by the posterior
pituitary gland, meaning damage to either of these structures can cause diabetes insipidus.
Causes of neurogenic diabetes insipidus include\:
Mutations in the vasopressin gene (e.g. autosomal dominant AVP-NPII)
Idiopathic (25% of cases)
Tumours\: pituitary adenomas or craniopharyngiomas/metastases
Trauma
Infections (e.g. meningitis)
Vascular (e.g. Sheehan's syndrome)
Sarcoidosis\: formation of granulomas in the pituitary gland.Haemochromatosis\: deposition of iron in the pituitary gland and hypothalamic tissue.
Nephrogenic diabetes insipidus¹
The kidneys are responsible for reabsorbing
binding or damages the kidneys has the potential to cause diabetes insipidus.
Causes of nephrogenic diabetes insipidus include\:
Mutations in the ADH receptor gene
Mutations in the aquaporin-2 gene (aquaporin 2 is responsible for reabsorption of water from the urine)
Metabolic - hypercalcaemia/hyperglycaemia/hypokalaemia
Drugs - lithium/demeclocycline - both interfere with the binding of ADH
Chronic renal disease
Amyloidosis
Post obstructive uropathy
Dipsogenic diabetes insipidus¹
Dipsogenic diabetes insipidus occurs as a result of hypothalamic disease or trauma. The hypothalamus is responsible for
controlling the thirst mechanism which is a key component of maintaining normovolaemia. In dipsogenic diabetes, the
thirst mechanism damaged, resulting in the a
patient, therefore, consumes large volumes of
Gestational diabetes insipidus
During pregnancy, the placenta produces vasopressinase which breaks down vasopressin. Gestational diabetes insipidus
is therefore thought to be caused by the overproduction of vasopressinase by the placenta causing a de
functional vasopressin.
Primary polydipsia
Primary polydipsia is characterised by an individual consuming large volumes of
volumes of dilute urine. The symptoms of primary polydipsia are therefore very similar to those of diabetes insipidus,
however, a
behavioural disorder.

Symptoms and signs

Symptoms
Typical symptoms of diabetes insipidus include\:
Excessive urination (>3L/24hrs)
Excessive thirst (especially for ice-cold water)
Nocturia
Dehydration - headache/dizziness/dry mouth
Signs
Typical clinical signs of diabetes insipidus include\:
Hypotension
Dilute urine
Signs of dehydration (dry mucous membranes, prolonged capillary re

Investigations

24-hour urine collection
24-hour urine collection should be performed to measure the amount of urine produced.
Diabetes insipidus typically involves the production of more than 3 litres of urine in a 24-hour period.Blood tests
Blood tests relevant to diabetes insipidus include\:
Plasma glucose (to help rule out diabetes mellitus)
U&Es\: to assess renal function and rule out electrolyte abnormalities
Urine speci
Simultaneous plasma and urine osmolality
Fluid deprivation test 2
The patient is deprived of
the table below for the interpretation of results).
MRI brain
pituitary tumour).
MRI imaging of the pituitary, hypothalamus and pineal gland is used to assess for cranial causes of diabetes insipidus (e.g.
Renal tract ultrasound
Renal tract ultrasound or intravenous pyelogram is used to assess for evidence of post-obstructive uropathy.

Diagnosis

The
nephrogenic).
The table below shows the likely underlying cause based on the results of the
1,2
Urine osmolality after
(mOsm/kg)
Urine osmolality after
desmopressin (mOsm/kg)
Likely diagnosis
\<300 >800 Neurogenic DI
\<300 \<300 Nephrogenic DI
>800 >800
Primary
polydipsia
Neurogenic diabetes insipidus
If the diagnosis is neurogenic DI the urine osmolality will be low after
given.
This is because neurogenic DI is caused by the lack of ADH production, therefore, giving a synthetic form of ADH such as
desmopressin normalises levels of the hormone resulting in the normalisation of serum and urine osmolality.
Nephrogenic diabetes insipidus
If the diagnosis is nephrogenic DI then the urine osmolality will remain low throughout regardless of desmopressin. This is
because the kidneys are unable to respond to either synthetic or endogenous ADH.
Primary polydipsia
If the diagnosis is primary polydipsia the urine osmolality will remain high after
desmopressin is given. This is because the patient's vasopressin axis is intact and otherwise completely normal.
Partial diabetes insipidus or polydipsiaIf the diagnosis is that of partial DI or polydipsia the picture may be mixed and further investigations are required.Management
Neurogenic diabetes insipidus
The primary issue in neurogenic DI is an endogenous de
ADH such as desmopressin is usually e
require ongoing monitoring due to the risks associated with desmopressin treatment (e.g. overdose results in
hyponatraemia). Typically, patients require serum sodium osmolality measuring every 1 to 3 months.
2
Nephrogenic diabetes insipidus
If daily urine volume is less than 4 litres/24hrs and the patient is not severely dehydrated, de
always necessary. Patients need access to drinking water and should be advised to drink enough to satisfy their thirst.
Metabolic abnormalities should be corrected if present and any medications that could be causing the problem should
also be stopped (e.g. lithium, demeclocycline). High dose desmopressin is sometimes used for mild-to-moderate cases of
nephrogenic DI.
2
Primary polydipsia
The underlying psychiatric disorder needs to be treated.

References

Dr Colin Tidy. Diabetes Insipidus. Patient.info. Published December 2015. Available from\: [LINK].
Saifan C, Nasr R, Mehta S, et al; Diabetes insipidus\: a challenging diagnosis with new drug therapies. ISRN Nephrol. 2013
Mar 242013\:797620. doi\: 10.5402/2013/797620. eCollection 2013. Available from\: [LINK].

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Contents

What is diabetes insipidus?
Normal physiology
Causes of diabetes insipidus
Symptoms and signs
Investigations
Diagnosis
ManagementSource\: geekymedics.com