For the disease most commonly associated with the generic term "diabetes", see
Diabetes mellitus.
Diabetes insipidus (DI) is a disease 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, or by an insensitivity of the kidneys to that
hormone. It can also be induced iatrogenically by the diuretic conivaptan.
Signs and symptoms
Excessive urination and extreme thirst (especially for cold 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.
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,
bicarbonate and calcium 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 osmolality and electrolyte levels are typically low.
A fluid deprivation test helps determine whether DI is caused by:
- excessive intake of fluid
- a defect in ADH production
- a defect in the kidneys' response to ADH
This test measures changes in body weight, urine output, and urine composition when fluids are withheld. 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.
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, 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.
There are several forms of DI:
- Central diabetes insipidus is due to damage to the hypothalamus or pituitary due to a tumor, stroke, 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 diabetes insipidus is due to the inability of the kidney to respond normally to ADH. There are hereditary
causes (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 and amphotericin B), as well as in polycystic kidney
disease (PKD) and sickle-cell disease, and electrolyte disturbances such as
hypokalaemia and hypercalcaemia. In some cases, no cause is found.
- Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus. 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 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. 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. 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
NDI; 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
- The public domain document "Diabetes Insipidus", NIH Publication No. 01-4620, December 2000.
External links
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Endocrine pathology:
endocrine diseases (E00-35, 240-259) |
| Thyroid |
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(Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves
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Euthyroid sick syndrome |
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disease/Sheehan's syndrome, Kallmann
syndrome, Growth hormone deficiency, Diabetes
insipidus) |
| Adrenal |
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(Nelson's syndrome, Pseudo-Cushing's
syndrome) - CAH (due to 21-hydroxylase deficiency) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency
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