Q & A: Diabetes Insipidus in a Hypothyroid Golden Retriever

I have an interesting situation with a dog with polyuria and polydipsia (PU/PD) that I have not seen before, and wonder if you can offer any insight.

My patient is a 7-year old, male neutered Golden Retriever-mix weighing 69 pounds who was diagnosed as being hypothyroid and has been on L-thyroxine replacement (Soloxine) for at least 5 years. He was recently diagnosed with diabetes insipidus (DI) because of signs of severe PU/PD and low urine specific gravity. The dog was examined by a neurologist, who found no neurological deficits. On MRI examination, the dog had no abnormal findings to explain the onset of DI (i.e, no hypothalamic or pituitary lesions or masses). 

He is now on Soloxine at a dosage of 0.7 mg twice daily (there has been no change in L-T4 dose for last year). For the DI, we have him on 0.01% desmopressin, with drops administered twice daily into the conjunctival sac (1 drop in morning and 2 drops in evening).

His owner reports he has been doing great in the last 3 to 4 months since he added the desmopressin. Recently, however, we rechecked a 6-hour post-pill serum T4 concentration and found that the value was high at 5.5 μg/dl (reference range, 1-4 μg/dl).

My questions are:

1. Can this be due to an interaction of desmopressin and L-thyroxine?
2. Is this a result of correcting/properly treating his diabetes insipidus and is this common?
3. Do we need to take any special factors into consideration with dosing either drug, or just lower his Soloxine as we would in other hypothyroid dogs getting routine T4 rechecks for proper dosing?
4. Is this just a coincidence and no known correlation?

My Response:

The main sign of hyperthyroidism in dogs is PU/PD so I'm be a bit worried that the thyroid hormone supplementation is causing the signs (1-4). You could drop the dose down a bit to see if that helps the PU/PD. After a week or so on the reduced dose of L-T4, you could try stopping the desmopressin for a couple of days and see if the PU/PD returns.

I don't know of any problems with concurrent use of desmopressin and thyroid hormone. But it is somewhat unlikely that a 7-year old dog would develop DI without the presence of any obvious pituitary or CNS pathology (1,2,4).

Many dogs with undefined PU/PD will respond to desmopressin but most of those dogs do not have DI. I'm not saying that we shouldn't use the desmopressin to control the signs, but DI is very unlikely.

Follow-up Question:

Thank you for your ideas, Dr. Peterson.

Do you mean that perhaps he was being overtreated for his hypothyroidism thus making him hyperthyroid leading to the PU/PD that initially caused us to diagnose the diabetes insipidus? I'm pretty sure that his T4 was in the normal range at that time. And now when we just tested him and discovered the T4 high, he is no longer PU/PD (since being on the desmopressin).

That is interesting that even dogs who do not truly have DI will respond to desmopressin. Will desmopressin eventually stop helping though? Or would you just keep him on it as long as it controls the severe PU/PD?

My Response:

Remember that when we are doing a post-pill T4, we are only doing a single spot check. That doesn't really indicate that is happening throughout the day.

In addition, the finding of a serum T4 value within the lab's reference range does not indicate what that particular dog's individual T4 normal range actually is — in other words, some dogs may be perfectly euthyroid having a serum T4 value of 4.5 μg/dl, whereas others may be clinically hyperthyroid with a serum T4 of 3.5 μg/dl.

And yes, most dogs that respond to desmopressin do not really have DI. As long as you and the client realize that, this is a pretty safe drug and it can be used to control PU/PD for long periods (and maybe forever).

Again, I'd still try cutting back on the L-T4 dose first -- why give desmopressin if we can figure out the real cause of the PU/PD?

References:

1. Peterson ME, Nichols R: Investigation of polyuria and polydipsia, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Third Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, pp 16-25, 2004.
2. Randolph JF, Nichols R, Peterson ME: Diseases of the hypothalamus and pituitary. In: Birchard SJ, Sherding RG (eds): Manual of Small Animal Practice (Third Edition), Philadelphia, Saunders Elsevier, pp 398-408, 2006.
3. Peterson ME: Hyperthyroidism and thyroid tumor in dogs. In: Melian C, Perez Alenza MD, Peterson ME, Diaz M, Kooistra H (eds): Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Multimedica, Barcelona, Spain, 2008, pp 113-125.
4. Nichols R, Peterson ME: Investigation of polyuria and polydipsia, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; 215-220.