Diabetes insipidus is due to a lack of antidiuretic hormone (ADH) or an inability of the kidneys to respond to ADH. It results in the production of large volumes of dilute urine, prompting affected animals to drink large amounts of water to compensate. Diagnosis typically involves a water deprivation test and assessment of the response to exogenous ADH. Treatment is aimed at controlling polyuria.
Diabetes insipidus is an endocrine disorder arising from a lack of either production of, or response to, arginine vasopressin (AVP), also called antidiuretic hormone (ADH). Depending on the cause, two main categories of diabetes insipidus are recognized in veterinary medicine: central diabetes insipidus and nephrogenic diabetes insipidus.
Etiology of Diabetes Insipidus in Animals
Central diabetes insipidus results from decreased secretion of ADH, which is produced by the supraoptic and paraventricular nuclei of the hypothalamus and released from the posterior pituitary gland.
The hypophyseal form of central diabetes insipidus develops as a result of compression and destruction of the pituitary pars nervosa, infundibular stalk, or supraoptic nucleus in the hypothalamus. 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.
Additional causes of central diabetes insipidus include parasite migration, local infection, and surgery affecting the hypophysis.
In contrast, nephrogenic diabetes insipidus results when the kidneys do not adequately respond to ADH. Nephrogenic diabetes insipidus can be congenital or acquired.
Primary nephrogenic diabetes insipidus is characterized by a congenital lack of ADH receptors or poor receptor response in target cells in the kidney.
Secondary nephrogenic diabetes insipidus arises from functional deficits resulting from treatment with certain drugs, as well as from various underlying disease conditions—including electrolyte disturbances, endotoxemia, hyperadrenocorticism, hyperthyroidism in cats, leptospirosis in dogs, liver disease, and pyelonephritis—which interfere with the normal interaction between ADH and renal tubular receptors.
Epidemiology of Diabetes Insipidus in Animals
Diabetes insipidus occurs infrequently in dogs, cats, and laboratory rats, and even more rarely in other animals.
There are no sex, age, or breed predilections.
Clinical Findings of Diabetes Insipidus in Animals
Animals with diabetes insipidus excrete large volumes of hypotonic urine and drink equally large amounts of water.
Diabetes insipidus causes inadequate urine concentration, even in the face of dehydration. With an absolute ADH deficiency or complete lack of response to ADH, there is persistent hyposthenuria (urine specific gravity [USG] ≤ 1.006). With partial ADH deficiency or an incomplete response to ADH, there is isosthenuria to minimal urine concentration (USG 1.008–1.020).
Urine osmolality is decreased below normal plasma osmolality (by approximately 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 of diabetes insipidus, but not in the nephrogenic form, is useful for clinical differentiation of the two forms of the disease.
Lesions
In neurohypophyseal central diabetes insipidus, the posterior lobe of the pituitary, infundibular stalk, and hypothalamus are compressed or disrupted by neoplastic cells. As a result, the nonmyelinated axons that transport ADH from its site of production (hypothalamus) to its site of release (pars nervosa) are interrupted.
Diagnosis of Diabetes Insipidus in Animals
Chronic polyuria
Water deprivation test and ADH response test
Response to exogenous AVP analogue administration
Diagnosis of diabetes insipidus is based on finding chronic polyuria that does not decrease with dehydration and is not due to primary renal disease.
Several tests can help confirm the diagnosis and differentiate central from primary or secondary nephrogenic diabetes insipidus or psychogenic polydipsia.Historically, diagnosis has been based on results of water deprivation testing and response to ADH administration. However, the test of choice is a therapeutic trial with desmopressin.
Gradual Water Deprivation Test
Water deprivation testing can be performed to evaluate the patient's ability to concentrate urine, provided that the animal is not dehydrated and does not have renal disease. Variations of the test protocol (referred to as the water deprivation test or modified water deprivation test) are described in the literature. An abrupt withdrawal of water is not recommended. Gradual water deprivation is preferred over complete withdrawal.
Pearls & Pitfalls
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Owners measure the volume of water consumed at home during an average 24-hour period each day for 3–5 consecutive days. From baseline, daily water allowance is restricted by 5%–10% each day, and body weight, hydration status, and USG (from the morning urine) are evaluated daily. Ideally, urine and plasma osmolality should be determined; however, because these tests are not readily available to most veterinarians, USG is typically monitored instead. The patient should be examined daily and monitored carefully to prevent a loss of > 5% body weight and severe dehydration.
End points of the test include the following:
USG > 1.025
5% dehydration (or loss of 5% of body weight)
daily water allowance < 60 mL/kg
A USG > 1.025 is suggestive of only partial ADH deficiency or antagonism to ADH action due to hypercortisolism or a diagnosis of psychogenic polydipsia as the cause of polyuria.
There is little change in specific gravity in animals with a complete lack of ADH activity, whether due to a primary loss of ADH or to unresponsiveness of the kidneys to ADH. In these cases, exogenous vasopressin is administered to evaluate for response.
ADH Response Test
An ADH response test should follow the water deprivation test to differentiate among conditions that can result in large volumes of urine that is chronically low in specific gravity but is otherwise normal. These conditions include nephrogenic diabetes insipidus (an inability of the kidneys to respond to ADH), psychogenic diabetes insipidus (polydipsia in response to a psychological disturbance but with a normal response to ADH), and hypercortisolism (which results in a partial deficiency of ADH activity because of the antagonistic effect of cortisol on ADH activity in the kidneys).
The ADH response test also can be used to evaluate animals in which a water deprivation test cannot be performed.
USG is determined at the start of the test.
Sterile desmopressin acetate is administered (2–4 drops in the conjunctival sac).
The bladder is emptied after 2 hours.
USG is measured at established intervals (4, 8, 12, 18, and 24 hours) after ADH administration.
Specific gravity peaks at > 1.026 in animals with a primary ADH deficiency, is markedly increased above the amount induced by water deprivation in animals with a partial deficiency in ADH activity, and shows little change in animals with nephrogenic diabetes insipidus. If the nasal solution is used, desmopressin must be passed through a 0.2-mcm sterilizing filter before application.
If osmolality is measured, the ratio of urine to plasma osmolality after water deprivation is > 3 in healthy animals, 1.8–3.0 in animals with moderate ADH deficiency, and < 1.8 in animals with severe deficiency. The ratio of urine to plasma osmolality after ADH administration, as compared with that after water deprivation, is > 2 in animals with primary ADH deficiency, 1.1–2.0 in animals with inhibitors to ADH action, and < 1.1 in animals unresponsive to ADH.
Therapeutic Trial With Desmopressin
The test of choice is a closely monitored therapeutic trial with desmopressin.
All other causes of polyuria/polydipsia should initially be excluded, limiting the differential diagnoses to central diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydipsia.
For cats, the owner should measure the animal’s 24-hour water intake 2–3 days before the therapeutic trial with desmopressin, allowing free-choice water intake.
Desmopressin acetate (0.1 mg/mL) is administered in the conjunctival sac (1–4 drops, every 12 hours) or given orally as tablets (0.1–0.2 mg, PO, every 12 hours) for 3–5 days.
A dramatic decrease in water intake (> 50%) during the first treatment day strongly suggests an ADH deficiency and a diagnosis of central diabetes insipidus or partial nephrogenic diabetes insipidus.
Other Testing
Diabetes insipidus also needs to be distinguished from other diseases involving polyuria. The most common are diabetes mellitus with glycosuria and high USG, and chronic nephritis with a USG that is usually low and shows evidence of renal failure (with proteinuria, urinary casts, etc).
If central diabetes insipidus is suspected, advanced imaging, such as CT or MRI, can reveal a pituitary mass.
Treatment of Diabetes Insipidus in Animals
Desmopressin acetate (central diabetes insipidus)
Thiazide diuretics
Chlorpropamide
Treatment of central diabetes insipidus is not always necessary, as long as free access to water is available and polyuria does not pose undue concern.
To manage polyuria, desmopressin acetate, a synthetic analogue of ADH, can be administered. The initial dose is 0.1 mg/mL nasal solution (2 drops) applied to the nasal mucosae or conjunctivae, or tablets given orally (0.1–0.2 mg/dog, PO, every 8–12 hours); this dose is gradually increased until the minimum effective dose is determined.
Maximal effect usually occurs in 2–6 hours and lasts for 10–12 hours. Water should not be restricted. Treatment should be continued every 12–24 hours for the life of the animal.
Chlorpropamide has also been used to stimulate ADH secretion in central diabetes insipidus.
No specific treatment for nephrogenic diabetes insipidus is available. Management involves addressing the underlying disease.
Thiazide diuretics (eg, chlorothiazide or hydrochlorothiazide) can be used to help manage polyuria in nephrogenic or central diabetes insipidus.
See Pharmacotherapeutics in Diabetes Insipidus in Animals for pharmacological considerations.
Key Points
Diabetes insipidus is rare in dogs and cats and results from deficiency of ADH or lack of response to ADH, or it can be secondary to brain trauma.
Diagnosis can be achieved through administration of a water deprivation test or by showing an increase in urine osmolality after ADH supplementation.
The primary treatment for central diabetes insipidus is desmopressin acetate, a synthetic analogue of ADH. Intranasal treatment can be effective for dogs.
For More Information
Peralta J, Labato MA. Central diabetes insipidus. Clinician’s Brief. June 2019.
Rossi TA, Ross LA. Diabetes insipidus. In: Rédei GP. Encyclopedia of Genetics, Genomics, Proteomics, and Informatics. Springer; 2008:498.
Nelson RW. Water metabolism and diabetes insipidus. In: Feldman EC, Nelson RW, Reusch CE, Scott-Moncrief JCR, Behrend NC. Canine and Feline Endocrinology. 4th ed. Elsevier/Saunders; 2015:1-36.
Also see pet owner content regarding diabetes insipidus in dogs and cats.
