Diabetes insipidus

Excessive urination and extreme thirst and increased fluid intake (especially for cold water and sometimes ice or ice water) are typical for DI.[6] 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 offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium that may lead to hypokalemia.[7]

The several forms of diabetes insipidus are:

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.[12]

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).

The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubules; specifically, it acts on proteins called aquaporins and more specifically aquaporin 2 in the following cascade. When released, ADH binds to V2 G-protein coupled receptors within the distal convoluted tubules, increasing cyclic AMP, which couples with protein kinase A, stimulating translocation of the aquaporin 2 channel stored in the cytoplasm of the distal convoluted tubules and collecting ducts into the apical membrane. These transcribed channels allow water into the collecting duct cells. The increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.

Nephrogenic DI results from lack of aquaporin channels in the distal collecting duct (decreased surface expression and transcription). It is seen in lithium toxicity, hypercalcemia, hypokalemia, or release of ureteral obstruction. Therefore, a lack of ADH prevents water reabsorption and the osmolarity of the blood increases. With increased osmolarity, the osmoreceptors in the hypothalamus detect this change and stimulate thirst. With increased thirst, the person now experiences a polydipsia and polyuria cycle.

Hereditary forms of diabetes insipidus account for less than 10% of the cases of diabetes insipidus seen in clinical practice.[13]

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.[14]

A fluid deprivation test is another way of distinguishing DI from other causes of excessive urination. If there is no change in fluid loss, giving desmopressin can determine if DI is caused by:

1. a defect in ADH production
2. a defect in the kidneys' response to ADH

This test measures the changes in body weight, urine output, and urine composition when fluids are withheld to induce dehydration. The body's 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 mOsm/kg with fluid restriction, while a stabilization at a lower level indicates diabetes insipidus.[15] Stabilization in this test means, more specifically, when the increase in urine osmolality is less than 30 Osm/kg per hour for at least three hours.[15] Sometimes measuring blood levels of ADH toward the end of this test is also necessary, but is more time-consuming to perform.[15]

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 person should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases urine osmolarity, the hypothalamic production of ADH is deficient, and the kidney responds normally to exogenous vasopressin (desmopressin). If the DI is due to kidney pathology, desmopressin does not change either urine output or osmolarity (since the endogenous vasopressin levels are already high).

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[16] as a marked absence of thirst even in response to hyperosmolality.[17] In some cases of adipsic DI, the person may also fail to respond to desmopressin.[18]

If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging, particularly a pituitary 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. Most people with this form have either experienced past head trauma or have stopped ADH production for an unknown reason.

Treatment involves drinking sufficient fluids to prevent dehydration.[1] Other treatments depend on the type.[1] In central and gestational DI treatment is with desmopressin.[1] Nephrogenic DI may be treated by addressing the underlying cause or the use of a thiazide, aspirin, or ibuprofen.[1]

The word "diabetes" (/ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɪs/) comes from Latin diabētēs, which in turn comes from Ancient Greek: διαβήτης, romanized: diabētēs, which literally means "a passer through; a siphon".[22] Ancient Greek physician Aretaeus of Cappadocia (fl. in the first century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease.[23][24] Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through",[22] which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go".[23] The word "diabetes" is first 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"—the full meaning is "lacking flavor or zest; not tasty". Application of this name to DI arose from the fact that diabetes insipidus does not cause glycosuria (excretion of glucose into the urine).

In a large survey conducted amongst patients with central diabetes insipidus, the majority were in favor of changing the disease's name to "vasopressin deficiency" to avoid confusion with diabetes mellitus.[5]

• Diabetes insipidus at Curlie