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Initial testing for adipsia involves electrolyte, blood urea nitrogen and creatinine levels, serum and urine osmolality, blood hormone levels, like vasopressin. In patients who have defects in thirst regulation and vasopresin secretion, serum vassopresin levels are low or absent. Measurements of urine electrolytes and osmolality are critical in determining the central, rather than renal, nature of the defect in water homeostasis. In adipsia, the fractional excretion of sodium is less than 1%, unless a coexisting defect in AVP secretion is present. In salt intoxication, the urine sodium concentrations are very high and fractional excretion of sodium is greater than 1%. Initial test results may be suggestive of diabetes insipidus. The circulating AVP levels tend to be high, which indicate an appropriate response of the pituitary to hyperosmolality. Patients may have mild stable elevations of serum sodium concentrations, along with elevations in both BUN and creatinine levels and in the BUN/creatinine ratio.
Type D is the least commonly diagnosed and researched type of adipsia. The AVP release in this subtype occurs with normally functioning levels of osmoregulation.
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 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 Osm/kg with fluid restriction, while a stabilization at a lower level indicates diabetes insipidus. 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. Sometimes measuring blood levels of ADH toward the end of this test is also necessary, but is more time consuming to perform.
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 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 renal 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 as a marked absence of thirst even in response to hyperosmolality. In some cases of adipsic DI, the patient may also fail to respond to desmopressin.
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.
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 isoosmolar is usually obtained before the patient becomes dehydrated.
Central DI and gestational DI respond to desmopressin which is given as intranasal or oral tablets. Carbamazepine, an anticonvulsive medication, has also had some success in this type of DI. Also, gestational DI tends to abate on its own four to six weeks following labor, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option.