Diabetes insipidus

2 Diagnosis

Diabetes insipidus (DI) is a condition characterized by

excessive thirst and excretion of large amounts of severely
dilute urine, with reduction of uid intake having no effect on the concentration of the urine.[1] There are different types of DI, each with a dierent set of causes.
The most common type in humans is the neurological
form, called central DI (CDI), which involves a deciency of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). The second common type of
DI is nephrogenic diabetes insipidus (NDI), which is due
to kidney or nephron dysfunction caused by an insensitivity of the kidneys or nephrons to ADH. DI can also be
gestational, or caused by alcohol or some types of drug
abuse. DI should not be confused with nocturia.

To distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and
calcium levels need to be tested. Measurement of blood
electrolytes can reveal a high sodium level (hypernatremia
as dehydration develops). Urinalysis demonstrates a dilute urine with a low specic gravity. Urine osmolarity
and electrolyte levels are typically low.
A uid deprivation test is another way of distinguishing
DI from other causes of excessive urination. It is also
used to help determine what DI is caused by:
1. a defect in ADH production

Although they have a common name, diabetes mellitus and diabetes insipidus are two entirely separate conditions with unrelated mechanisms. Both cause large
amounts of urine to be produced (polyuria), and the
term diabetes is derived from the Greek word meaning
siphon. However, diabetes insipidus is either a problem
with the production of antidiuretic hormone (central diabetes insipidus) or kidneys response to antidiuretic hormone (nephrogenic diabetes insipidus), whereas diabetes
mellitus causes polyuria via a process called osmotic diuresis, due to the high blood sugar leaking into the urine
and taking excess water along with it.

2. a defect in the kidneys response to ADH

This test measures the changes in body weight, urine output, and urine composition when uids are withheld to
induce dehydration. The bodys normal response to dehydration is to conserve water by concentrating the urine.
Those with DI continue to urinate large amounts of dilute
urine in spite of water deprivation. In primary polydipsia,
the urine osmolality should increase and stabilize at above
280 Osm/kg with uid restriction, while a stabilization at
a lower level indicates diabetes insipidus.[4] Stabilization
The number of new cases of diabetes insipidus each year in this test means, more specically, when the increase
in urine osmolality is less than 30 Osm/kg per hour for
is 3 in 100,000.[2]
at least 3 hours.[4] Sometimes measuring blood levels of
ADH toward the end of this test is also necessary, but is
more time consuming to perform.[4]

Signs and symptoms

To distinguish between the main forms, desmopressin

stimulation is also used; desmopressin can be taken by
injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink uids or water only when
thirsty and not at other times, as this can lead to sudden uid accumulation in the central nervous system. If
desmopressin reduces urine output and increases urine
osmolarity, the hypothalamic production of ADH is decient, and the kidney responds normally to exogenous vasopressin (desmopressin). If the DI is due to renal pathology, desmopressin does not change either urine output or
osmolarity (since the endogenous vasopressin levels are
already high).

Excessive urination and also extreme thirst (especially for

cold water and sometimes ice or ice water) are typical for
DI.[3] The symptoms of excessive urination and extreme
thirst are similar to what is seen in untreated diabetes mellitus, with the distinction that the urine does not contain
glucose. Blurred vision is a rarity. Signs of dehydration
may also appear in some individuals, since the body cannot conserve much (if any) of the water it takes in.
Extreme urination continues throughout the day and the
night. In children, DI can interfere with appetite, eating,
weight gain, and growth, as well. They may present with
fever, vomiting, or diarrhea. Adults with untreated DI
may remain healthy for decades as long as enough water
is consumed to oset the urinary losses. However, there
is a continuous risk of dehydration and loss of potassium
that may lead to hypokalemia.

Whilst Diabetes Insipidus usually occurs with polydipsia,

it can also rarely occur not only in the absence of polydipsia but in the presence of its opposite, Adipsia (or hypodipsia). Adipsic diabetes insipidus is recognised[5]
as a marked absence of thirst even in response to
1

CLASSIFICATION

hyperosmolality.[6] In some cases of Adipsic DI, the patient may also fail to respond to desmopressin.[7]

channels allow water into the collecting duct cells. The

increase in permeability allows for reabsorption of water
If central DI is suspected, testing of other hormones of into the bloodstream, thus concentrating the urine.
the pituitary, as well as magnetic resonance imaging, par- Nephrogenic results from lack of Aquaporin channels in
ticularly a Pituitary MRI, is necessary to discover if a the distal collecting duct (decreased surface expression
disease process (such as a prolactinoma, or histiocytosis, and transcription). It is seen in Lithium toxicity, hypersyphilis, tuberculosis or other tumor or granuloma) is af- calcemia, hypokalemia or release of ureteral obstruction.
fecting pituitary function. Most people with this form Hereditary forms of diabetes insipidus account for less
have either experienced past head trauma or have stopped than 10% of the cases of diabetes insipidus seen in clinical
ADH production for an unknown reason.
practice.[8]
Habit drinking (in its severest form termed psychogenic
polydipsia) is the most common imitator of diabetes insipidus at all ages. While many adult cases in the medical
4 Classication
literature are associated with mental disorders, most patients with habit polydipsia have no other detectable disease. The distinction is made during the water depriva- The several forms of DI are:
tion test, as some degree of urinary concentration above
isoosmolar is usually obtained before the patient becomes
4.1 Neurogenic
dehydrated.
Main article: Neurogenic diabetes insipidus

Pathophysiology

Electrolyte and volume homeostasis is a complex mechanism that balances the bodys requirements for blood
pressure and the main electrolytes sodium and potassium.
In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however,
the body will retain water at the expense of deranging
electrolyte levels.
The regulation of urine production occurs in the
hypothalamus, which produces ADH in the supraoptic
and paraventricular nuclei. After synthesis, the hormone
is transported in neurosecretory granules down the axon
of the hypothalamic neuron to the posterior lobe of the
pituitary gland, where it is stored for later release. In addition, the hypothalamus regulates the sensation of thirst
in the ventromedial nucleus by sensing increases in serum
osmolarity and relaying this information to the cortex.
Neurogenic/central DI results from a lack of ADH; occasionally it can present with decreased thirst as regulation
of thirst and ADH production occur in close proximity in
the hypothalamus. It is encountered as a result of hypoxic
encephalopathy, neurosurgery, autoimmunity or cancer,
or sometimes without an underlying cause (idiopathic).

Neurogenic diabetes insipidus, more commonly known as

central diabetes insipidus, is due to the lack of vasopressin
production in the hypothalamus due to a range of causes.
The underlying causes of Central DI can include vascular,
autoimmune, infection, sarcoidosis, some drugs, surgery,
head trauma, benign or metastatic pituitary-hypothalamic
tumor (particularly originating from breast and lung), although 50% of cases are found to be idiopathic.

4.2 Nephrogenic
Main article: Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus is due to the inability of
the kidney to respond normally to vasopressin.

4.3 Dipsogenic

Dipsogenic DI or primary polydipsia results from excessive intake of uids as opposed to deciency of arginine
vasopressin. It may be due to a defect or damage to the
thirst mechanism, located in the hypothalamus;[9] or due
The main eector organ for uid homeostasis is the to mental illness. Treatment with DDAVP may lead to
kidney. ADH acts by increasing water permeability in water intoxication.
the collecting ducts and distal convoluted tubules; specifically, it acts on proteins called aquaporins and more
specically aquaporin 2 in the following cascade. When 4.4 Gestational
released, ADH binds to V2 G-protein coupled receptors within the distal convoluted tubules, increasing cyclic Gestational DI occurs only during pregnancy and the
AMP, which couples with protein kinase A, stimulating postpartum period. During pregnancy, women produce
translocation of the aquaporin 2 channel stored in the vasopressinase in the placenta, which breaks down ADH.
cytoplasm of the distal convoluted tubules and collect- Gestational DI is thought to occur with excessive producing ducts into the apical membrane. These transcribed tion and/or impaired clearance of vasopressinase.[10]

3
Most cases of gestational DI can be treated with desmo- treatment for this condition.[12]
pressin (ddAVP), but not vasopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.
6 Etymology
Diabetes insipidus is also associated with some serious
diseases of pregnancy, including pre-eclampsia, HELLP
syndrome and acute fatty liver of pregnancy. These cause
DI by impairing hepatic clearance of circulating vasopressinase. It is important to consider these diseases if a
woman presents with diabetes insipidus in pregnancy, because their treatments require delivery of the baby before
the disease will improve. Failure to treat these diseases
promptly can lead to maternal or perinatal mortality.

5
5.1

Treatment
Central DI

Central DI and gestational DI respond to desmopressin

which is given as intranasal or oral tablets.
Carbamazepine, an anticonvulsive medication, has
also had some success in this type of DI. Also, gestational DI tends to abate on its own four to six weeks
following labor, though some women may develop it
again in subsequent pregnancies. In dipsogenic DI,
desmopressin is not usually an option.

The word diabetes (/da.bitiz/ or /da.bits/)

comes from Latin diabts, which in turn comes from
Ancient Greek (diabts) which literally means
a passer through; a siphon".[13] Ancient Greek physician
Aretaeus of Cappadocia (. in the rst century CE)
used that word, with the intended meaning excessive discharge of urine, as the name for the disease.[14][15] Ultimately, the word comes from Greek (diabainein), meaning to pass through,[13] which is composed of - (dia-), meaning through and
(bainein), meaning to go.[14] The word diabetes is rst
recorded in English, in the form diabete, in a medical
text written around 1425.
Insipidus comes from Latin language insipidus (tasteless), from Latin: in- not + sapidus tasty from sapere
have a taste - meaning lacking avor or zest; not tasty.
This is because diabetes insipidus has no glycosuria (excretion of glucose into urine).

7 References
Using Wikipedia for research

5.2

Nephrogenic DI

Desmopressin will be ineective in nephrogenic DI and

is treated by reversing the underlying cause (if possible) and replacing the free water decit. The diuretic
hydrochlorothiazide (a thiazide diuretic) or indomethacin
can be used to create mild hypovolemia which encourages salt and water uptake in proximal tubule and thus
improve nephrogenic diabetes insipidus. Amiloride has
additional benet of blocking Li uptake. Thiazide diuretics are sometimes combined with amiloride to prevent
hypokalemia. It seems paradoxical to treat an extreme
diuresis with a diuretic, and the exact mechanism of action is unknown but the thiazide diuretics will decrease
distal convoluted tubule reabsorption of sodium and water, thereby causing diuresis. This decreases plasma volume, thus lowering the glomerular ltration rate and enhancing the absorption of sodium and water in the proximal nephron. Less uid reaches the distal nephron, so
overall uid conservation is obtained.[11]
Lithium-induced nephrogenic DI may be eectively
managed with the administration of amiloride, a
potassium-sparing diuretic often used in conjunction
with thiazide or loop diuretics. Clinicians have been
aware of lithium toxicity for many years, and traditionally
have administered thiazide diuretics for lithium-induced
polyuria and nephrogenic diabetes insipidus. However,
amiloride has recently been shown to be a successful

[1] Tamparo, Carol (2011). Fifth Edition : Diseases of the

Human Body. Philadelphia, PA: F.A. Davis Company. p.
288. ISBN 978-0-8036-2505-1.
[2] Saborio P, Tipton GA, Chan JC (2000). Diabetes
Insipidus. Pediatrics in Review 21 (4): 122129.
doi:10.1542/pir.21-4-122. PMID 10756175.
[3] USE. Diabetes insipidus - PubMed
Ncbi.nlm.nih.gov. Retrieved 2012-05-28.

Health.

[4] Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up

to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
[5] Crowley RK, Sherlock M, Agha A, Smith D, Thompson CJ (2007). Clinical insights into adipsic diabetes
insipidus: a large case series. Clin. Endocrinol. (Oxf)
66 (4): 47582. doi:10.1111/j.1365-2265.2007.02754.x.
PMID 17371462.
[6] Sinha A, Ball S, Jenkins A, Hale J, Cheetham T (2011).
Objective assessment of thirst recovery in patients with
adipsic diabetes insipidus. Pituitary 14 (4): 30711.
doi:10.1007/s11102-011-0294-3. PMID 21301966.
[7] Smith D, McKenna K, Moore K, Tormey W, Finucane
J, Phillips J, Baylis P, Thompson CJ (2002). Baroregulation of vasopressin release in adipsic diabetes insipidus. J. Clin. Endocrinol. Metab. 87 (10): 45648.
doi:10.1210/jc.2002-020090. PMID 12364435.

[8] Fujiwara TM, Bichet DG (2005). Molecular Biology of Hereditary Diabetes Insipidus. Journal of the
American Society of Nephrology 16 (10): 28362846.
doi:10.1681/ASN.2005040371. PMID 16093448.
[9] Perkins RM, Yuan CM, Welch PG (March 2006). Dipsogenic diabetes insipidus: report of a novel treatment
strategy and literature review. Clin. Exp. Nephrol.
10 (1): 637. doi:10.1007/s10157-005-0397-0. PMID
16544179.
[10] Kalelioglu I, Kubat Uzum A, Yildirim A, Ozkan T,
Gungor F, Has R (2007). Transient gestational diabetes insipidus diagnosed in successive pregnancies:
review of pathophysiology, diagnosis, treatment, and
management of delivery. Pituitary 10 (1): 8793.
doi:10.1007/s11102-007-0006-1. PMID 17308961.
[11] Long J (November 2004). Paradoxical antidiuretic effect of thiazides in diabetes insipidus: another piece in
the puzzle. J. Am. Soc. Nephrol. 15 (11): 2948
50. doi:10.1097/01.ASN.0000146568.82353.04. PMID
15504949.
[12] Finch CK, Kelley KW, Williams RB (April 2003).
Treatment of lithium-induced diabetes insipidus
with amiloride. Pharmacotherapy 23 (4): 54650.
doi:10.1592/phco.23.4.546.32121. PMID 12680486.
[13] Oxford English Dictionary. diabetes. Retrieved 2011-0610.
[14] Harper, Douglas (20012010). Online Etymology Dictionary. diabetes.". Retrieved 2011-06-10
[15] Dallas, John (2011). Royal College of Physicians of Edinburgh. Diabetes, Doctors and Dogs: An exhibition on
Diabetes and Endocrinology by the College Library for
the 43rd St. Andrews Day Festival Symposium

External links
Diabetes insipidus at DMOZ

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