Tuesday, February 15, 2011

How Do We Confirm a Diagnosis of Hypothyroidism in Dogs?

Because of the vague clinical signs and the absence of specific abnormalities on a routine blood test, the diagnosis should be confirmed through a specific evaluation of the thyroid gland. As always, laboratory results should be interpreted in the light of history and physical examination findings. A thorough clinical examination of the patient, knowledge of the advantages and disadvantages of all available tests and knowledge of the factors that can influence the results, will allow the veterinarian to correctly diagnose the disease.

In dogs with suspected hypothyroidism, the clinical suspicion of the disease is obtained by reviewing the dog’s signalment, history, and clinical features. A general blood screening examination, including a CBC, comprehensive chemical panel, and complete urinalysis are next done to look for changes consistent with hypothyroidism and exclude other problems that mimic hypothyroidism.

If hypothyroidism is still suspected, the diagnosis should be confirmed through a specific evaluation of the thyroid gland function. These tests include measurement of serum concentrations of total and free T4, T3, and TSH. The choice of diagnostic test(s) performed are based heavily on the index of suspicion for hypothyroidism.

In some dogs, it may also be necessary to use thyroid scintigraphy to definitely confirm the condition. However, most veterinary offices do not have the equipment needed to do this thyroid scanning procedure.

Thyroid specific evaluation

Total thyroxine (T4)
This test usually used as the initial thyroid specific screening test. If the results of this test are within normal limits, your veterinarian will usually look for other causes of your dog’s clinical signs. Most dogs with hypothyroidism will have low values for T4 compared with healthy dogs. However, dogs that have other diseases can also have low T4, so false-positive T4 results are commonly observed. Again, that is why general laboratory testing must be done in all dogs with suspected hypothyroidism.

This test measures the total amount of thyroxine (abbreviated T4, because it contains 4 iodine molecules) which is the main hormone produced by the thyroid gland. hormone circulating in the blood, which includes both bound and unbound T4 molecules. More than 99% of T4 hormone is “bound,” meaning that it is attached to proteins in the blood, making the bound T4 too big to pass from the circulation into the tissues. A T4 result by itself is can be misleading, inasmuch as it is affected by anything that changes the amount of binding proteins circulating in the blood, such as occurs with drugs and nonthyroidal illness.

Certain kinds of drugs (e.g. sulfa antibiotics, anti-inflammatory, anti-depressant and anti-seizure medication) can cause artificially lowered thyroid levels so it is important to make sure we account for these before making a diagnosis.

In addition, although normal T4 reference levels of healthy adult dogs tend to be similar for most breeds, they do vary depending on age and breed. Puppies, for example, display higher T4 levels than adult dogs, because their bodies need extra hormones as they undergo the maturation process. Compared to the adult dog “normal range,” the optimal thyroid levels for puppies are normally in the high-normal to slightly high range. Conversely, the basal metabolism of geriatric dogs is usually slowing, so optimal T4 levels are likely to be closer to midrange or even slightly lower. Similarly, giant breed dogs have lower basal T4 levels, and Sight hounds as a group have the lowest T4 levels of all the breed categories.

Free T4
Serum free T4 represents the tiny fraction (< 0.1%) of total T4 that is unbound and therefore is biologically active and able to enter the tissues. Since protein levels in the blood do not (or only minimally) affect free T4, it is considered a more accurate test of true thyroid activity than the total T4. Free T4 is much less likely to be influenced by nonthyroidal illness or drugs.

Both total T4 and free T4 are lowered in almost all dogs of hypothyroidism. While most endocrinologists favor the equilibrium dialysis method for measuring free T4, newer technologies offer alternative and accurate assays that are faster and less costly.

Overall, this is a more sensitive indicator of hypothyroidism. Some dogs that are not truly hypothyroid may have a low total T4 but a normal free T4.

Total T3
Measuring serum T3 alone is not considered an accurate method of diagnosing hypothyroidism, as this hormone reflects tissue thyroid activity and is often influenced by concurrent nonthyroidal illness. It is, however, useful as part of a thyroid profile or health screening panel.

Thyroid stimulating hormone (TSH)
Production of thyroid hormones is regulated by the pituitary gland, through a hormone called thyroid-stimulating hormone (TSH). A feedback loop exists between the body and the pituitary gland, with TSH production by the pituitary going up when the body needs thyroid hormone and turning off when thyroid hormone levels are high.

Therefore, dogs with primary hypothyroidism are expected to have high serum TSH concentrations. Unfortunately, the current TSH test used in dogs is associated with a high incidence of false-negative or false-positive results.

Result for serum TSH must be evaluated together with serum T4 (and free T4) concentrations. Finding a low T4, low free T4, and a high TSH concentration is diagnostic for canine hypothyroidism. On the other hand, finding a high TSH level together with normal values for T4 or free T4 does not confirm hypothyroidism and is best ignored (at least for the time being).

Thyroglobulin autoantibody levels
High titers of thyroglobulin autoantibodies are present in the serum of dogs with autoimmune thyroiditis, which is the heritable form of hypothyroidism. Performing this test is especially important in screening breeding stock for autoimmune thyroiditis, as dogs testing positive for thyroglobulin autoantibodies should not be bred.

This is not in any way a stand-alone test for hypothyroidism and evaluation of additional tests is necessary to determine whether a dog is hypothyroid.

Thyroid Scintigraphy (Scanning)
Thyroid scintigraphy provides valuable information regarding both thyroid anatomy and physiology and can play an integral role in the diagnosis of thyroid disease in dogs or cats. Although rarely used to diagnose hypothyroidism, is now clear that thyroid imaging is also the best way to confirm the diagnosis of that common disorder. At the Animal Endocrine Clinic, we have the equipment needed to perform thyroid scintigraphy and we readily use this in the diagnosis of dogs and cats with thyroid disease. For more information about thyroid scans, please visit our Nuclear Imaging Facebook page.

In normal dogs, the thyroid gland appears on thyroid scans as two well-defined, focal (ovoid) areas of uptake in the cranial to middle cervical region. The two thyroid lobes are symmetrical in size and shape and are located side by side. Activity in the normal thyroid closely approximates activity in the salivary glands, with an expected “brightness” ratio of 1:1.

In dogs with hypothyroidism, thyroid scanning typically reveals decreased or even absent thyroid uptake (thyroid gland is not at all visible on the scan). In contrast, dogs that have falsely low serum thyroid hormone concentrations secondary to illness or drug therapy have a normal thyroid image.


Anonymous said...

We have a 9-year-old beagle mix- spayed female, who has recently been critically anemic. She had a dx of cytopenia early in Jan. & has responded to treatments of prednisone & doxycycline so that her counts are mostly normal now except for her PCV which is still low (although gradually improving). Routine blood work showed v. low T4 levels so I requested a full thyroid panel.

Total & free T3 & T4 are all very low, but TSH level is mid-range (13- with ref. range given as 0-37). I don't know if her medications or prior anemia could cause artificially low readings, or if this is genuine hypothyroidism. She also has- to complicate matters- a gallstone with elevated liver enzymes. Any thoughts on this? I can't currently reach our dog's vet to discuss the panel.

I was intrigued by the claim that free T4 is the best indication of true hypothyroidism- free T4 tested at 4 (with ref. range of 8-26) & total T4= 1 with a reference range of 15-67.

Dr. Mark E. Peterson said...

Despite the low total and free T4 values in your dog, there are a number of reasons why hypothyroidism is unlikely.
• First of all, severe anemia and cytopenia are not generally part of the clinical picture of hypothyroidism.
• Secondly, any critical illness such as severe anemia can falsely lower both the total and free T4 values.
• Thirdly, many drugs, but especially glucocorticoids such as prednisone, are well know to falsely lower both the total and free T4 values.

Does your dog have any clinical signs consistent with hypothyroidism, such as hair loss or hyperlidipemia?

Anonymous said...

Thanks for your response- I really appreciate the help.

I guess the thing I'm trying to wrap my head around is the idea of false results. When you say the results are falsely lowered, does that mean her actual values are probably normal, but for some reason, the bloodwork is reporting at a value that is lower than normal?

Or would it be more accurate to say that her thyroid levels genuinely are low, but the cause of the low levels is not primary hypothyroidism? And if that is the case, would supplementation be warranted?

As for symptoms, I'm not sure- she has a very heavy coat & sheds a lot, but it's not thin or patchy. She was about 50 pounds a couple of years ago, and we had reduced her food intake so that she was at a better (we thought) weight for her. Since she isn't pure beagle, it's hard to judge what her ideal weight should be, but 40 seemed lean, but not scrawny. Since she's been on the prednisone, she's lost some more weight & looks scawny now, although her beaglish appetite hasn't waned, even when her PCV was about 9%. She is always v. hungry on the pred, but I guess it has sped up her metabolism so that she isn't keeping her weight on. And we're feeding her more now, on her vet's advice.

Her face/muzzle seems droopy now, and I read that that can be a sign of hypothyroidism. And she definitely has muscle wasting & increased weakness- especially in her hindlegs.

My concern is that she may be in need of supplementation, and that need could be masked by her other issues. Do you think a therapeutic trial on thyroid could be warranted? Or might that be dangerous?

Dr. Mark E. Peterson said...

The problem with running blood tests to diagnose hypothyroidism is that what really matters is what is going on within the cells -- not in the bloodstream. So when a dog develops a concurrent disease or illness (or when a dog is treated with glucocorticoids), the circulating levels of thyroid hormone generally fall. This could be due to a drop in the levels (IN THE BLOOD) but the cellular levels tend to remain normal. In most cases, the free T4 remains normal, especially if the problem is only with thyroid hormone binding to plasma proteins in the circulation.

This situation is quite variable between dogs, illnesses, and drugs used. It is very complicated and still remains poorly understood. It's been shown in many human studies that supplementation with thyroid hormone is of little to no benefit. But I'm not all convinced that a therapeutic trial does any harm.

I think it's highly unlikely that your dog is hypothyroid. That said, one can never be 100% sure that trial therapy will not help so you may want to talk to your vet about it.

Serpy said...

I know this is an old post, but thought I would ask a question here and see. I have a 13 year old mixed breed 60 lb male dog. In April at a checkup the doc told me his thyroid was low and described the symptoms I might be seeing. The only one we identified with was the fact that our dog was overweight. Per the vets advice we began administering him soloxine and retested his blood 6 weeks later. They said the levels of t4 were now ideal and we went about our lives. Over 6 months he lost 5 pounds but is otherwise exactly the same. Then a few weeks ago we noticed blood at the end of his urination stream. They did an ultrasound and say he has a bladder tumor. I can't help but wonder if there is any relationship to the new medication. Any chance the meds could be causing the bladder issue? I read the medication insert and its very non specific with side effects. What would happen if I took him off the soloxine? I know he's an old man and this could be coincidental but I don't want to make any assumptions.
Thank you.

Dr. Mark E. Peterson said...

It's highly unlikely that there is any relationship to either the low serum T4 value or the L-thyroxine (Soloxine) supplementation to his bladder cancer. I've never seen it happen and it's not been reported.

I would NOT recommend stopping the thyroid medicine at this time. That might only make him feel worse.

Vishal said...

my 1.5 yr old beagle has the following values:

FT3: 243 pg/dl
FT4: 0.69 ng/dl
TSH: 0.002uIU/ml

Does he have thyroid problems. He sleeps quite a bit and likes to sit in the sun, even during summers.

Dr. Mark E. Peterson said...

What are the reference intervals for the 3 thyroid hormones? I'm not familiar with those units. Were these tests done in veterinary laboratory?

What were the results of the routine tests? Was anemia present? High cholesterol?

Unknown said...

This is a super old post, but I'd like to give it a shot since you, Dr Peterson, seem to actually be answering questions. My vet said that my dog has a hypothyroid. She was tested for T3, T4, and free T4. The only chart that I've found shows her at normal ranges. She is 12 and a half and part wolf hound, which I have read can have lower levels.
She tested:
T3- 54 vets range= 90 -180
T4- 1.3 vets range= 1.6- 5.0
Free T4- 1.4 vets range= 1.3- 3.0
As stated above. The normal ranges that I found, a he is right on. Especially the T3. I found average ranges between 30 and 70. Besides being sleepy, I don't see any other symptoms. Shes almost 13. She hasn't taken any medications, and I cooked for her for 8 years. She is now on taste of the wild and raw meat. I am just really interested if these ranges are correct. She is parent according to the chart I found. Thank you in advance if you see this.

Dr. Mark E. Peterson said...

Not diagnostic to me. At least add on a TSH level, as described above.

Buza Victoria said...

Hello Dr. Peterson,
I would like to ask you why TT4 and TT3 concentrations in some dogs with pronounced clinical signs of hypothyroidism still remain within the normal values? I searched for it everywhere but wasn't able to find something.
Thank you in advance.

Dr. Mark E. Peterson said...

Very rare to have normal T4 values in dogs with severe clinical signs. In man, >90% of patient have normal levels of T4 and free T4 (but with high TSH), likely because the patients are diagnosed earlier than in most dogs.

Buza Victoria said...

Thank you a lot