Classification & external resources

ICD-10	E23.2 N25.1
ICD-9	253.5 588.1
DiseasesDB	3639
MedlinePlus	000377 Central000460 Congenital000461 Nephrogenic ''000511
eMedicine	med/543  ped/580
MeSH	D003919

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:

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. 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

• The Diabetes Insipidus Foundation, Inc

•  • [ e] Endocrine pathology: endocrine diseases (, )
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
Pancreas	Diabetes mellitus (type 1, type 2, coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy) - Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome
Parathyroid	Hypoparathyroidism (Pseudohypoparathyroidism) - Hyperparathyroidism (Primary, Secondary, Tertiary)
Pituitary	hyperfunction (Acromegaly, Hyperprolactinaemia, Syndrome of inappropriate antidiuretic hormone) - Hypopituitarism (Sheehan's syndrome, Kallmann syndrome, Simmonds' disease, Growth hormone deficiency) - Diabetes insipidus - Hypothalamic-pituitary dysfunction
Adrenal	Cushing's syndrome (Nelson's syndrome, Pseudo-Cushing's syndrome) - Congenital adrenal hyperplasia (due to 21-hydroxylase deficiency) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency (Addison's disease) - Hypoaldosteronism
Gonads	Polycystic ovary syndrome - 5-alpha-reductase deficiency - Hypogonadism - Delayed puberty - Precocious puberty
Other	Autoimmune polyendocrine syndrome - Carcinoid syndrome - Laron syndrome - Multiple endocrine neoplasia - Psychogenic dwarfism - Androgen insensitivity syndrome - Progeria

•  • [ e] Health science - Medicine - Urinary system - Pathology - Nephrology (, )
Diseases of the glomerulus	Glomerulonephritis - Focal segmental glomerulosclerosis - Membranoproliferative glomerulonephritis - Membranous glomerulonephritis - Nephritic syndrome - Post-streptococcal glomerulonephritis - Nephrotic syndrome (Minimal change disease) - IgA nephropathy - Lupus nephritis - Diabetic nephropathy
Tubulointerstitial diseases of the kidney	Interstitial nephritis - Pyelonephritis - Hydronephrosis - Pyonephrosis - Balkan nephropathy - Reflux nephropathy
Renal failure	Acute renal failure - Chronic renal failure
Diseases of the renal tubule and other disorders of kidney and ureter	tubule (Fanconi syndrome - renal tubular acidosis - renal cell carcinoma - pseudohypoaldosteronism) - Renal osteodystrophy - Nephroptosis - Ureterocele
Other diseases and disorders of urinary system	Cystitis (Interstitial cystitis, Trigonitis) - Neurogenic bladder - Vesicointestinal fistula - Urethritis - Urethral stricture - Urinary tract infection - Kidney stone
Tumours of the kidney	Renal cell carcinoma - Wilms' tumor (children)
See also conditions (, )