Differentiating Diabetes Insipidus from Psychogenic Polydipsia in Dogs

My problem case is a  7-year old male-neutered Labrador retriever-mix that presented to me for moderate to severe polyuria and polydipsia (PU/PD).  While doing well at home, his owner did mention he also has had some recent weight gain (current weight is 29 kg). He has a history of arthritis, which the owner is treating with some type of holistic supplementation.

I did a CBC and complete biochemistry profile, with all values being within normal range. Results of complete thyroid panel (serum T4, T3, free T4, and TSH) also showed that all values were within the reference intervals.  

Urine was collected by cystocentesis for complete urinalysis and urine culture and susceptibility. The urinalysis showed a specific gravity of 1.010, with a normal sediment; the urine culture was negative. A urine cortisol:creatinine ratio was also normal.

We next performed serial measurements for urine specific gravity over a 24-hour period. The results are listed below:

• 6:30 AM 1.028 
• 3:15 PM 1.004
• 6:15 PM 1.000
• 8:10 PM 1.005
• 6:30 AM 1.019

The water consumption measured over this 24-hour period was 96 ounces (2.9 liters), which appears to be in quite high for a dog of this weight.

On an abdominal ultrasound examination, the liver, adrenal glands, bladder, and kidneys were all found to be normal.  

At this time, I've excluded the common rule outs for PU/PD, including Cushing's disease, kidney disease, diabetes mellitus, hypercalcemia, liver disease, and hyperthyroidism. My two major rule outs are either psychogenic polydipsia or diabetes insipidus (DI).

My questions:

1. Have we sufficiently ruled out diabetes insipidus based on the higher morning urine specific gravities?
2. Could this dog still be suffering from psychogenic polydipsia?
3. Any other possibilities or suggestions?

My Response:

Differential diagnoses for
polyuria & polydipsia in dogs

Your dog certainly doesn't have complete central or nephrogenic diabetes insipidus (DI). He could have partial DI, but from the history, psychogenic polydipsia (compulsive water drinking) is a major rule out (1-3).

Whenever we see such wide fluctuations in urine specific gravity measurement, we must move a behavioral problem to near the top of our differential list.

My biggest concern is that we don't want to miss a serious cause of PU/PD, such as occult pyelonephritis— remember that you have collected urine from the bladder for culture, so it's still possible that the dog has an infection in the kidneys that is difficult to detect.

There are a number of ways we could proceed at this point, but this step-wise approach is what I'd recommend.

Step 1 — Stop all supplements: First, I'd start by stopping the holistic supplements for a couple of weeks to see if that helps.  If they are giving the dog any other drugs or supplements, they should all be discontinued, at least temporarily. It is unlikely that these supplements are the problem, but we don't always know what compounds holistic or herbal supplements contain or what effects they will have on an individual dog.

Step 2—Rule out atypical leptospirosis: If no improvement is seen after discontinuing the holistic supplements, I'd next consider leptospirosis serology and urine PCR testing (4-6). Occasionally, we see an atypical form of leptospirosis in dogs that present with a relatively acute onset PU/PD, hyposthenuria or isosthenuria, but no other laboratory abnormalities (azotemia does not generally develop in these dogs). The urine concentration defect is thought to be an acquired form of nephrogenic DI (3).

In dogs not previously vaccinated for leptospirosis, Leptospira infection can be confirmed by positive leptospirosis serology or use of molecular detection of leptospiral DNA by PCR testing of urine samples. In dogs previously vaccinated for leptospirosis, a 4-fold rise in convalescent titers is often diagnostic of the atypical form of this disease.

Step 3— Rule out occult pyelonephritis: If testing for atypical leptospirosis is negative, then I'd next do an antibiotic trial for 2 weeks to rule out occult pyelonephritis (3).

The antibiotics that I would recommend for this trial are either enrofloxacin (Baytril) at the dosage of 10 mg/kg/day or amoxicillin/clavulanic acid (Clavamox) at the dosage of 12.5 mg/kg/day. Since this is a relatively large dog, generic ciprofloxacin would be a cheaper alternative than brand-name enrofloxacin. The dose of ciprofloxacin, however, is 1.5-2 times greater than Baytril because of poorer intestinal absorption of the drug (7).

If the dog's PU/PD markedly diminishes during the antibiotic trial period, then we can make a presumptive diagnosis of occult pyelonephritis.  In that case, the antibiotic treatment would be extended for a full 6-week period.

Step 4— Do water deprivation test: If we see no clinical response to the antibiotic treatment, then I'd go on and do a water deprivation test next. The water deprivation test is generally considered by most authorities to be the best diagnostic test for differentiating between central DI, nephrogenic DI, and psychogenic polydipsia. However, the classical water deprivation test is labor-intensive, difficult to perform correctly, unpleasant for the dog, relies heavily on repeated emptying of the bladder, and can lead to untoward complications and misdiagnosis in some animals (3).

What I'd recommend in this dog is to first do an abbreviated, overnight water deprivation test. With this method, the owner walks the dog late at night to empty the bladder, and the dog is then put in a room (or a cage) overnight without access to water. The first thing the next morning (before the dog is given any food or water), the owner again walks the dog and collects a urine sample.  The urine sample should then be dropped off at your office so you can measure the urine specific gravity after the overnight water deprivation. If the sample is concentrated (> 1.030-1.035), then we can rule out partial DI, leaving us with a diagnosis of psychogenic polydipsia (1-3).

Step 5— Evaluate the response to desmopressin:  If the dog fails to adequately concentrate after the overnight water deprivation test, you could do an official, in-hospital water deprivation test. However, I'd try a desmopressin trial to evaluate the response instead (3,8).

If the desmopressin does work to control the PU/PD and to raise the urine specific gravity, that is consistent with partial DI (either central or nephrogenic DI).  On the other hand, if desmopressin fails to have any effect on the water consumption or urination in this dog, that would be most consistent with psychogenic polydipsia (compulsive water drinking).

References:

1. Dunn JK. The dog with polydipsia and polyuria In: Torrance AG, Mooney CT, eds. BSAVA Manual of Small Animal Endocrinology. 2nd ed. Shurdington, Cheltenham: British Small Animal Veterinary Association, 1998;3-9.
2. Nichols R. Polyuria and polydipsia. Diagnostic approach and problems associated with patient evaluation. Vet Clin North Am Small Anim Pract 2001;31:833-844.
3. Nichols, R., Peterson ME. Investigation of polyuria and polydipsia In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Gloucester: British Small Animal Veterinary Association, 2012;215-220.
4. Harkin KR, Roshto YM, Sullivan JT. Clinical application of a polymerase chain reaction assay for diagnosis of leptospirosis in dogs. J Am Vet Med Assoc 2003;222:1224–1229
5. Greene CE, Sykes JE, Brown CA et al. Leptospirosis. In: Infectious Diseases of the Dog and Cat, 3rd edn. 2006;402–417.  
6. Van De Maele I, Claus A, Haesebrouck F, et al. Leptospirosis in dogs: a review with emphasis on clinical aspects. Vet Rec 2008;163:409–413.
7. Papich MG. Ciprofloxacin pharmacokinetics and oral absorption of generic ciprofloxacin tablets in dogs. Am J Vet Res 2012;73:1085-1091.
8. Nichols R, Hohenhaus AE. Use of the vasopressin analogue desmopressin for polyuria and bleeding disorders. J Am Vet Med Assoc 1994;205:168-173.