Central diabetes insipidus is caused by reduced secretion ofantidiuretic hormone (ADH). When target cells in the kidney lack the biochemical machinery necessary to respond to the secretion of normal or increased circulating levels of ADH, nephrogenic diabetes insipidus results. It occurs infrequently in dogs, cats, and laboratory rats, and rarely in other animals.

Etiology

The hypophyseal form develops as a result of compression and destruction of the pars nervosa, infundibular stalk, or supraoptic nucleus in the hypothalamus. The lesions responsible for the disruption of ADH synthesis or secretion in hypophyseal diabetes insipidus include large pituitary neoplasms (endocrinologically active or inactive), a dorsally expanding cyst or inflammatory granuloma, and traumatic injury to the skull with hemorrhage and glial proliferation in the neurohypophyseal system.

Clinical Findings

Affected animals excrete large volumes of hypotonic urine and drink equally large amounts of water. Urine osmolality is decreased below normal plasma osmolality (~300 mOsm/kg) in both hypophyseal and nephrogenic forms, even if the animal is deprived of water. The increase of urine osmolality above that of plasma in response to exogenous ADH in the hypophyseal form, but not in the nephrogenic form, is useful in the clinical differentiation of the 2 forms of the disease.

Lesions

The posterior lobe, infundibular stalk, and hypothalamus are compressed or disrupted by neoplastic cells. This interrupts the nonmyelinated axons that transport ADH from its site of production (hypothalamus) to its site of release (pars nervosa).

Diagnosis

This is based on chronic polyuria that does not respond to dehydration and is not due to primary renal disease. To evaluate the ability to concentrate urine, a water deprivation test should be done if the animal is not dehydrated and does not have renal disease. The bladder is emptied, and water and food are withheld (usually 3–8 hr) to provide a maximum stimulus for ADH secretion. The animal should be monitored carefully to prevent a loss of >5% body wt and severe dehydration. Urine and plasma osmolality should be determined; however, because these tests are not readily available to most practitioners, urine specific gravity is frequently used instead. At the end of the test, urine specific gravity is >1.025 in those animals with only a partial ADH deficiency or with antagonism to ADH action caused by hypercortisolism. There is little change in specific gravity in those animals with a complete lack of ADH activity, whether due to a primary loss of ADH or to unresponsiveness of the kidneys.

An ADH response test should follow to differentiate among conditions that may result in large volumes of urine that is chronically low in specific gravity but otherwise normal. These include nephrogenic diabetes insipidus (an inability of the kidneys to respond to ADH), psychogenic diabetes insipidus (a polydipsia in response to some psychological disturbance but a normal response to ADH), and hypercortisolism (which results in a partial deficiency of ADH activity due to the antagonistic effect of cortisol on ADH activity in the kidneys). This test also can be used to evaluate animals in which a water deprivation test could not be performed. Urine specific gravity is determined at the start of the test; desmopressin acetate is administered (2–4 drops in the conjunctival sac); the bladder is emptied at 2 hr; and urine specific gravity is measured 4, 8, 12, 18, and 24 hr after ADH administration. Specific gravity peaks at >1.026 in animals with a primary ADH deficiency, is significantly increased above the level induced with water deprivation in those with a partial deficiency in ADH activity, and shows little change in those with nephrogenic diabetes insipidus.

If osmolality is measured, the ratio of urine to plasma osmolality after water deprivation is >3 in normal animals, 1.8–3 in those with moderate ADH deficiency, and <1.8 in those with severe deficiency. The ratio of urine osmolality after ADH administration as compared with water deprivation is >2 in animals with primary ADH deficiency, between 1.1 and 2 in those with inhibitors to ADH action, and <1.1 in those unresponsive to ADH.

As an alternative to the water deprivation test, or in cases in which this test fails to establish a definitive diagnosis, a closely monitored therapeutic trial with desmopressin (see below) can be performed. Again, all other causes of polyuria and polydipsia should initially be ruled out, limiting the differential diagnosis to central diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydipsia. For cats, the owner should measure the animal's 24-hr water intake 2–3 days before the therapeutic trial with desmopressin, allowing free-choice water intake. The intranasal preparation of desmopressin is administered in the conjunctival sac (1–4 drops, bid) for 3–5 days. A dramatic reduction in water intake (>50%) during the first treatment day would strongly suggest an ADH deficiency and a diagnosis of central diabetes insipidus or partial nephrogenic diabetes insipidus.

Diabetes insipidus also needs to be distinguished from other diseases with polyuria. The most common are diabetes mellitus with glycosuria and high urine specific gravity, and chronic nephritis with a urine specific gravity that is usually low and shows evidence of renal failure (protein, casts, etc).

Treatment

Polyuria may be controlled using desmopressin acetate, a synthetic analog of ADH. The initial dose is 2 drops applied to the nasal mucosae or conjunctivae; this is gradually increased until the minimal effective dose is determined. Maximal effect usually occurs in 2–6 hr and lasts for 10–12 hr. Water should not be restricted. Treatment should be continued sid or bid for the life of the animal.

Last full review/revision July 2011 by Deborah S. Greco, DVM, PhD, DACVIM; Janice E. Kritchevsky, 'VMD, MS, DACVIM