Diabetes Insipidus

ADH, or vasopressin, is important in maintaining water balance and blood pressure in the body. ADH is produced in the hypothalamus and transported to the posterior pituitary (neurohypophysis) through the pituitary stalk. Osmoreceptors near the hypothalamus detect changes in osmotic concentration of extracellular fluids and release or withhold ADH accordingly. Concentrated ECF stimulates ADH secretion and dilute ECF inhibits ADH secretion. Also, stretch receptors in the right atrium are excited by overfilling, which inhibits ADH secretion, while underfilling of the right atrium stimulates ADH release. High concentrations of ADH increase arterial pressure by constricting arterioles throughout the body, which helps explain its alternate name, vasopressin. In the absence of ADH, the collecting tubules and ducts of the kidneys become almost impermeable to water, preventing reabsorption of water and allowing extreme water loss into the urine.

Central diabetes insipidus (CDI) is the partial or complete lack of ADH production by the hypothalamus. Primary nephrogenic diabetes insipidus (NDI) is the partial or complete lack of response of the renal tubules to ADH. Secondary or acquired NDI is antagonism or unresponsiveness of the interaction between ADH and its receptors in the renal tubules. The latter relates to an underlying disease, and recovery usually occurs if the disease is successfully treated. For example, pyometra causes acquired NDI due to release of bacterial endotoxin which competes with ADH for binding sites on the renal tubular membranes. When the pyometra is treated, the renal tubular insensitivity to ADH is reversed.

Most dogs and cats consume less than 60 mL of water/kg body weight daily, and drinking more than 100 mL/kg represents polydipsia. Polyuria accompanies polydipsia and a USG of <1.030 would be expected. Although renal failure is associated with isosthenuria (USG of 1.008 – 1.012), diabetes insipidus is generally associated with dilute (hyposthenuric) urine (USG <1.008). When polydipsia and polyuria have been confirmed, there is no evidence of underlying disease based on clinical and laboratory findings, and the urine is dilute, differential diagnoses are CDI, NDI, and psychogenic polydipsia.

Modified water deprivation test

A modified water deprivation test (see Chapter 7: Renal System) can be performed to assist in making the diagnosis. Often access to water is gradually restricted for 3-5 days prior to the deprivation test in order to restore the renal corticomedullary concentration gradient, which may be impaired by chronic polydipsia and polyuria. The goal of this phase of the test is to decrease the 24 hour water intake to 100 mL/kg body weight or less on the day prior to the water deprivation test. However, animals should be monitored for weight loss, dehydration, and azotemia during this phase of the test as it may not be possible for the animal to raise the USG at all and dehydration can occur quickly. If the test proceeds, water is then completely withheld after emptying the bladder, weighing the animal, measuring serum urea, creatinine, and sodium, and determining USG and urine osmolality. The endpoint of the test is loss of 3-5% body weight, clinical dehydration or illness, development of azotemia, or development of concentrated urine (USG >1.030 for dogs, >1.035 for cats; osmolality >1100 mOsm/kg, for dogs and cats). Plasma can be collected for ADH concentration at this point.

Normal animals and animals with psychogenic polydipsia will concentrate their urine with water deprivation and no further testing is necessary. Animals with complete CDI will have no change in their USG and osmolality will not exceed plasma osmolality (280 – 310 mOsm/kg). In animals with CDI, ADH administration at the endpoint of the test results in significant increases in USG and osmolality (by 50-600%). If partial CDI is present, urine osmolality will be greater than 300 mOsm/kg with mild dehydration, but a further increase of 10-50% occurs with ADH administration. Animals with NDI are unable to concentrate their urine with mild dehydration and fail to respond to injected ADH. Endogenous ADH concentrations at the endpoint of the water deprivation test will be normal to high in normal animals, animals with psychogenic polydipsia, and animals with NDI. Endogenous ADH concentrations will be low in animals with CDI.