Diabetes insipidus
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For the disease most commonly associated with the generic term "diabetes", see
Diabetes mellitus.
Diabeted insipidus
Classification and external resources
Vasopressin
ICD-10 E23.2 N25.1
ICD-9 253.5 588.1
OMIM 304800 125800
DiseasesDB 3639
MedlinePlus 000377
Central000460
Congenital000461
Nephrogenic 000511
eMedicine med/543 ped/580
MeSH D003919
Diabetes insipidus (DI) (Greek διαβαίνειν diabainein - to pass through and Latin
insipidus - without taste) is a condition characterized by excretion of large
amounts of severely diluted urine, which cannot be reduced when fluid intake is
reduced. It denotes inability of the kidney to concentrate urine. DI is caused
by a deficiency of antidiuretic hormone (ADH), also known as vasopressin, due to
the destruction of the back or "posterior" part of the pituitary gland where
vasopressin is normally released from, or by an insensitivity of the kidneys to
that hormone. It can also be induced iatrogenically by various drugs.
Contents
[hide]
* 1 Signs and symptoms
* 2 Diagnosis
* 3 Pathophysiology
* 4 Classification
o 4.1 Cranial diabetes insipidus
o 4.2 Nephrogenic
o 4.3 Dipsogenic
o 4.4 Gestational
* 5 Treatment
* 6 Sources
* 7 External links
Signs and symptoms
Excessive urination and extreme thirst (especially for cold water and sometimes
ice or ice water) are typical for DI. Symptoms of diabetes insipidus are quite
similar to those of untreated diabetes mellitus, with the distinction that the
urine is not sweet as it does not contain glucose and there is no hyperglycemia
(elevated blood 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.
The 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 drunk to offset the
urinary losses. However, there is a continuous risk of dehydration.
Diagnosis
In order 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 specific gravity.
Urine osmolarity and electrolyte levels are typically low.
A fluid deprivation test helps determine whether DI is caused by:
1. excessive intake of fluid
2. a defect in ADH production
3. a defect in the kidneys' response to ADH
This test measures changes in body weight, urine output, and urine composition
when fluids are withheld and as dehydration occurs. The body's normal response
to dehydration is to concentrate urine and conserve water, so urine becomes more
concentrated and urination becomes less frequent. Those with DI continue to
urinate large amounts of dilute urine in spite of not drinking any fluids.
Sometimes measuring blood levels of ADH during this test is also necessary.
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 fluids or water only when thirsty and not
at other times, as this can lead to sudden fluid accumulation in central nervous
system. If desmopressin reduces urine output and increases osmolarity, the
pituitary production of ADH is deficient, and the kidney responds normally. If
the DI is due to renal pathology, desmopressin does not change either urine
output or osmolarity.
If central DI is suspected, testing of other hormones of the pituitary, as well
as magnetic resonance imaging (MRI), is necessary to discover if a disease
process (such as a prolactinoma, or histiocytosis, syphilis, tuberculosis or
other tumor or granuloma) is affecting pituitary function. Thankfully most
people with this form either have experienced past head trauma or simply have
stopped ADH production for no apparent reason.
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 literature are associated with mental disorders, most patients with
habit polydipsia have no other detectable disease. The distinction is made
during the water deprivation test, as some degree of urinary concentration above
isosmolar is usually obtained before the patient becomes dehydrated.
Pathophysiology
Electrolyte and volume homeostasis is a complex mechanism that balances the
body's 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
antidiuretic hormone (ADH or vasopressin) 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.
The main effector organ for fluid homeostasis is the kidney. ADH acts by
increasing water permeability in the collecting ducts and distal convoluted
tubule, specifically it acts on proteins called aquaporins which open to allow
water into the collecting duct cells. This increase in permeability allows for
reabsorption of water into the bloodstream, thus concentrating the urine.
Classification
There are several forms of DI:
Cranial diabetes insipidus
Cranial diabetes insipidus (sometimes central or neurogenic DI) is due to damage
to the hypothalamus or pituitary due to a tumor, trauma (such as a fracture to
the base of the skull), stroke,[1] neurosurgery or some rather rare causes
(which include hemochromatosis, sarcoidosis, histiocytosis, diseases that can
form masses in the vicinity like a tuberculoma or syphilis and some genetic
disorders). If the hypothalamus is damaged, the feeling of thirst may be
completely absent.
Nephrogenic
Nephrogenic diabetes insipidus is due to the inability of the kidney to respond
normally to ADH.
* There are hereditary causes. Inherited forms have been associated with AVPR2
(X-linked)[2] and AQP2 (autosomal).[3]. Approximately 90% are due to mutations
of the ADH V2 receptor, and 10% mutations of the aquaporin 2 water channel), but
these are rare (incidence is around 4 per million live births). Most are male,
because V2 receptor mutations are x-linked recessive defects.
* More common are acquired forms of NDI, which occur as a side-effect to some
medications (such as lithium citrate[4] and amphotericin B), as well as in
polycystic kidney disease (PKD) and sickle-cell disease, and electrolyte
disturbances such as hypokalemia[5][6] and hypercalcemia.[6] In some cases, no
cause is found.
Dipsogenic
Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is
located in the hypothalamus[7]. This defect results in an abnormal increase in
thirst and fluid intake that suppresses ADH secretion and increases urine
output. Desmopressin is ineffective, and can lead to fluid overload as the
thirst remains.
Gestational
Gestational DI only occurs during pregnancy. While all pregnant women produce
vasopressinase in the placenta, which breaks down ADH, this can assume extreme
forms in GDI. [8]
Most cases of gestational DI can be treated with desmopressin. In rare cases,
however, an abnormality in the thirst mechanism causes gestational DI, and
desmopressin should not be used.
Treatment
Central DI and gestational DI respond to desmopressin. Carbamazepine, an
anti-convulsive medication, has also had some success in this type of DI. Also
gestational DI tends to abate on its own 4 to 6 weeks following labour, though
some women may develop it again in subsequent pregnancies. In dipsogenic DI,
desmopressin is not usually an option.
Desmopressin will be ineffective in nephrogenic DI. Instead, the diuretic
hydrochlorothiazide (HCT or HCTZ) or indomethacin can improve nephrogenic
diabetes insipidus; HCT is sometimes combined with amiloride to prevent
hypokalemia. Again, adequate hydration is important for patients with DI, as
they may become dehydrated easily.
Sources
1. ^ Sweeney AT, Blake MA, Adelman LS, et al (2004). "Pituitary apoplexy
precipitating diabetes insipidus". Endocr Pract 10 (2): 135–8. PMID 15256331.
http://aace.metapress.com/openurl.asp?genre=article&issn=1530-891X&volume=10&issue=2&spage=135.
2. ^ Online 'Mendelian Inheritance in Man' (OMIM) DIABETES INSIPIDUS,
NEPHROGENIC, X-LINKED -304800
3. ^ Online 'Mendelian Inheritance in Man' (OMIM) DIABETES INSIPIDUS,
NEPHROGENIC, AUTOSOMAL -125800
4. ^ Christensen S, Kusano E, Yusufi AN, Murayama N, Dousa TP (June 1985).
"Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of
lithium in rats". J. Clin. Invest. 75 (6): 1869–79. doi:10.1172/JCI111901. PMID
2989335.
5. ^ Marples D, Frøkiaer J, Dørup J, Knepper MA, Nielsen S (April 1996). "Hypokalemia-induced
downregulation of aquaporin-2 water channel expression in rat kidney medulla and
cortex". J. Clin. Invest. 97 (8): 1960–8. doi:10.1172/JCI118628. PMID 8621781.
6. ^ a b Carney S, Rayson B, Morgan T (October 1976). "A study in vitro of the
concentrating defect associated with hypokalaemia and hypercalcaemia". Pflugers
Arch. 366 (1): 11–7. PMID 185584.
7. ^ 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): 63–7. doi:10.1007/s10157-005-0397-0. PMID 16544179. http://dx.doi.org/10.1007/s10157-005-0397-0.
8. ^ 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): 87–93. doi:10.1007/s11102-007-0006-1. PMID 17308961. http://dx.doi.org/10.1007/s11102-007-0006-1.
* The public domain document "Diabetes Insipidus", NIH Publication No. 01-4620,
December 2000.
External links
* The Diabetes Insipidus Foundation, Inc
* Information on Diabetes Insipidus
[show]
v • d • e
Endocrine pathology: endocrine diseases (E00-35, 240-259)
Pancreas/
glucose
metabolism
Diabetes mellitus types: (type 1, type 2, MODY), complications: (coma,
angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy)
Hypoglycemia · Hyperinsulinism · Zollinger-Ellison syndrome · insulin receptor (Rabson-Mendenhall
syndrome) · Insulin resistance
Hypothalamic/
pituitary axes
Pituitary
Hyperpituitarism (Acromegaly, Hyperprolactinaemia, SIADH)
Hypopituitarism (Sheehan's syndrome, Kallmann syndrome, Growth hormone
deficiency, Diabetes insipidus)
Adiposogenital dystrophy · Empty sella syndrome · Pituitary apoplexy · ACTH
deficiency
Thyroid
Hypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre,
Myxedema)
Hyperthyroidism (Graves disease, Toxic multinodular goitre, Teratoma with
thyroid tissue or Struma ovarii)
Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's
thyroiditis)
Euthyroid sick syndrome · Thyroid hormone resistance · Thyroid nodule
Parathyroid
Hypoparathyroidism (Pseudohypoparathyroidism) · Hyperparathyroidism (Primary,
Secondary, Tertiary)
Adrenal
Adrenocortical hyperfunction: Cushing's syndrome (Nelson's syndrome,
Pseudo-Cushing's syndrome) · Hyperaldosteronism (Conn syndrome, Bartter
syndrome) · Glucocorticoid remediable aldosteronism
CAH (Lipoid, 3β, 11β, 17α, 21α)
Adrenal insufficiency (Addison's disease, Waterhouse-Friderichsen syndrome) ·
Hypoaldosteronism
Gonads
ovarian (Polycystic ovary syndrome, Premature ovarian failure)
testicular (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase
deficiency) · Androgen receptor (Androgen insensitivity syndrome)
general (Hypogonadism, Delayed puberty, Precocious puberty)
Height
Gigantism · Dwarfism/Short stature (Laron syndrome, Psychogenic dwarfism)
Thymus
Abscess of thymus · Thymus hyperplasia
Multiple
Autoimmune polyendocrine syndrome · Carcinoid syndrome · Multiple endocrine
neoplasia (1, 2) · Progeria · Woodhouse-Sakati syndrome
see also congenital, neoplasia
[show]
v • d • e
Urinary system · Pathology · Urologic disease / Uropathy (N00-N39, 580-599)
Abdominal
Nephropathy/
(nephritis+
nephrosis)
Glomerulopathy/
glomerulitis/
(glomerulonephritis+
glomerulonephrosis)
By appearance
Non-proliferative
.0 Minimal change · .1 Focal segmental · .2 Membranous
Proliferative
.3 Mesangial proliferative · .4 Endocapillary proliferative .5/.6
Membranoproliferative/mesangiocapillary · .7 Rapidly progressive/crescentic
By syndrome
Nephritic syndrome · Nephrotic syndrome
By condition
IgA/Berger's · Diabetic · Post-streptococcal · Lupus · Amyloidosis
Tubulopathy/
tubulitis
Proximal
RTA (RTA 2)
Thick ascending
Bartter syndrome
Distal convoluted
Gitelman syndrome
Collecting duct
Liddle's syndrome · RTA (RTA 1) · Nephrogenic diabetes insipidus
Renal papilla
Renal papillary necrosis
Major calyx/pelvis
Hydronephrosis · Pyonephrosis · Reflux nephropathy
Any/all
Acute tubular necrosis
Interstitium
Interstitial nephritis (Pyelonephritis, Danubian endemic familial nephropathy)
Any/all
General syndromes
Renal failure (Acute renal failure, Chronic renal failure)
Vascular
Renal artery stenosis · Hypertensive nephropathy · Renovascular hypertension
Other
Analgesic nephropathy · Renal osteodystrophy · Nephroptosis ·
Abderhalden-Kaufmann-Lignac syndrome
Ureter
Ureteritis · Ureterocele · Megaureter
Pelvic
Bladder
Cystitis (Interstitial cystitis, Trigonitis) · Neurogenic bladder ·
Vesicointestinal fistula · Vesicoureteral reflux
Urethra
Urethritis (Non-gonococcal urethritis) · Urethral syndrome · Urethral stricture
Any/all
Obstructive uropathy · Urinary tract infection · Retroperitoneal fibrosis ·
Urolithiasis (Kidney stone, Renal colic)
See also congenital, neoplasia, symptoms/signs
[show]
v • d • e
Sex linkage: X-linked recessive disorders
Immune
Chronic granulomatous disease (CYBB) · Wiskott-Aldrich syndrome · X-linked
Severe Combined Immunodeficiency · X-linked agammaglobulinemia · Hyper-IgM
syndrome type 1 · IPEX
Hematologic
Haemophilia A · Haemophilia B · X-linked sideroblastic anemia · X-linked
lymphoproliferative disease
Endocrine
Androgen insensitivity syndrome/Kennedy disease · Diabetes insipidus
Metabolic
amino acid: Ornithine transcarbamylase deficiency · Oculocerebrorenal syndrome
dyslipidemia: Adrenoleukodystrophy
carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency · Pyruvate
dehydrogenase deficiency · Danon disease/glycogen storage disease Type IIb
lipid storage disorder: Fabry's disease
mucopolysaccharidosis: Hunter syndrome
purine-pyrimidine metabolism: Lesch-Nyhan syndrome
mineral: Menkes disease
Nervous system
X-Linked mental retardation: Coffin-Lowry syndrome · Fragile X syndrome · MASA
syndrome · Rett syndrome
eye disorders: Color blindness (red and green, but not blue) · Ocular albinism
(1) · Norrie disease · Choroideremia
other: Charcot-Marie-Tooth disease (CMTX2-3) · Pelizaeus-Merzbacher disease
Skin
Dyskeratosis congenita · Hypohidrotic ectodermal dysplasia (EDA) · X-linked
ichthyosis
Neuromuscular
Becker's muscular dystrophy/Duchenne · Centronuclear myopathy · Myotubular
myopathy · Conradi-Hünermann syndrome
Urologic
Alport syndrome · Dent's disease
No primary system
Barth syndrome · McLeod syndrome · Simpson-Golabi-Behmel syndrome
Note: there are very few X-linked dominant disorders. These include X-linked
hypophosphatemia, Focal dermal hypoplasia, Aicardi syndrome, Incontinentia
pigmenti, and CHILD.
Retrieved from "http://en.wikipedia.org/wiki/Diabetes_insipidus"
Categories: Endocrinology | Nephrology | Diabetes
* This page was last modified on 6 January 2009, at 23:47.
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