Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst.
Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses.
[citation needed][9] The several forms of diabetes insipidus are: Central (or Neurogenic) DI has many possible causes.
According to the literature, the principal causes of central DI and their oft-cited approximate frequencies are as follows:[citation needed] Nephrogenic diabetes insipidus is due to the inability of the kidney to respond normally to vasopressin.
[10] Dipsogenic DI or primary polydipsia results from excessive intake of fluids as opposed to deficiency of arginine vasopressin.
When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.
[15] 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.
It is encountered as a result of hypoxic encephalopathy, neurosurgery, autoimmunity or cancer, or sometimes without an underlying cause (idiopathic).
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.
[citation needed] Nephrogenic DI results from a lack of aquaporin channels in the distal collecting duct (decreased surface expression and transcription).
Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops).
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).
Most people with this form have either experienced past head trauma or have stopped ADH production for an unknown reason.
[citation needed] Desmopressin will be ineffective in nephrogenic DI which is treated by reversing the underlying cause (if possible) and replacing the free water deficit.
A thiazide diuretic, such as chlorthalidone or hydrochlorothiazide, can be used to create mild hypovolemia which encourages salt and water uptake in proximal tubule and thus improve nephrogenic diabetes insipidus.
This decreases plasma volume, thus lowering the glomerular filtration rate and enhancing the absorption of sodium and water in the proximal nephron.
Clinicians have been aware of lithium toxicity for many years, and traditionally have administered thiazide diuretics for lithium-induced polyuria and nephrogenic diabetes insipidus.
Application of this name to DI arose from the fact that diabetes insipidus does not cause glycosuria (excretion of glucose into the urine).