Showing posts with label t3. Show all posts
Showing posts with label t3. Show all posts

Thursday, June 11, 2015

Diagnosing Hypothyroidism in Dogs


I have a 7-year old spayed Golden Retriever who weighs about 110 lbs. No signs of hypothyroidism except for being overweight with a borderline high serum cholesterol concentrations (256 mg/dl). The serum T4 value was slightly low at 0.9 µg/dl (reference interval, 1.0-4.0 µg/dl).

Is this slightly low serum T4 concentration diagnostic for hypothyroidism? Would you start her on levothyroxine (L-T4) and retest T4 levels in a month?

I'd appreciate your thoughts and recommendations.

My Response: 

I would never base the diagnosis on only a resting serum T4 value alone. We commonly find low values that fluctuate in and out of the reference range in dogs that are clinically normal and never develop hypothyroidism. In addition, most non-thyroidal illness will lower the total T4 values in dogs, and these dogs would not benefit from thyroid hormone supplementation (1). It certainly doesn't sound like your dog is sick or acting ill in any way, so this latter explanation probably doesn't apply here.

For your dog, I'd recommend that your veterinarian collect more sera to do a complete thyroid panel, which should include the following tests (2-4):
  • Serum T4 concentration
  • Serum T3 concentration
  • Serum free T4 by dialysis
  • Serum TSH concentration
  • Serum levels of thyroglobulin autoantibodies
If you have it available in your area, thyroid scintigraphy (nuclear medicine scan) is actually the best and most accurate way to diagnose hypothyroidism in dogs (4.5).

 References: 
  1. Kantrowitz LB, Peterson ME, Melian C, et al. Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease. J Am Vet Med Assoc 2001;219:765-769. 
  2. Peterson ME, Melian C, Nichols R. Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. J Am Vet Med Assoc 1997;211:1396-1402.  
  3. Nachreiner RF, Refsal KR, Graham PA, et al. Prevalence of serum thyroid hormone autoantibodies in dogs with clinical signs of hypothyroidism. J Am Vet Med Assoc 2002;220:466-471. 
  4. Diaz Espineira MM, Mol JA, Peeters ME, et al. Assessment of thyroid function in dogs with low plasma thyroxine concentration. J Vet Intern Med 2007;21:25-32.  
  5. Shiel RE, Pinilla M, McAllister H, et al. Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs. J Small Anim Pract 2012;53:278-285. 

Friday, September 16, 2011

Hyperthyroid in Cats: Table of Contents

As you know if you have been following this blog, I've spent much of the last few months writing about issue of hyperthyroidism, the most common endocrine disorder of the cat.

Before I move on to the topics of treatment of this common feline condition, I thought I'd post links to the topics I've covered thus far:
  1. Do All Hyperthyroid Cats Have a Thyroid Tumor? Is It Thyroid Cancer?
  2. Why Has Hyperthyroidism in Cats Reached Epidemic Levels?
  3. Top 10 Signs of Hyperthyroidism in Cats
  4. Top 12 Physical Exam Findings in Cats with Hyperthyroidism
  5. Diagnosing Hyperthyroidism in Cats: Routine Testing Procedures
  6. Diagnosis of Hyperthyroidism in Cats: Serum T4 Concentrations
  7. Diagnosis of Hyperthyroidism in Cats: Serum T3 Concentrations
  8. Diagnosis of Hyperthyroidism in Cats: Serum Free T4 Concentrations
  9. Diagnosis of Hyperthyroidism in Cats: Serum Free T4 (Part 2)
  10. Diagnosis of Hyperthyroidism in Cats: Serum Free T3 Concentrations
  11. Diagnosis of Hyperthyroidism in Cats: Serum TSH Concentrations
  12. Diagnosis of Hyperthyroidism: T3 Suppression Test
  13. Diagnosis of Hyperthyroidism: TRH Stimulation Test
  14. Diagnosis of Hyperthyroidism: Thyroid Scintigraphy
I'm halfway through with this "book" on feline hyperthyroidism!

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.

Monday, May 10, 2010

What is T4? How is the T4 Test Used to Diagnose Hyperthyroidism in my Cat?

What is being tested?
This test measures the amount of thyroxine, more commonly referred to as T4 or total T4, in your cat’s blood. T4 is one of two major iodine-containing hormones produced by the thyroid gland (the other is called triiodothyronine, or T3). The thyroid is a small, bi-lobed gland located just below the Adam's apple. This gland plays a vital role in controlling the rate at which the body uses energy or controls metabolism. Important components of the T4 and T3 molecules include the amino acid tyrosine and iodine (see Figure 1).

Figure 1

T4 makes up nearly 90% of the circulating thyroid hormones, while T3 makes up less than 10%. Inside the thyroid gland, T4 is bound to a protein called thyroglobulin. When the body requires thyroid hormone, the thyroid gland releases stored T4 into circulation. In the blood, T4 is either free (not bound) or protein-bound (primarily bound to serum protein). The concentration of free T4 is less than 0.1% of that of total T4. T4 is converted into T3 in the liver or other tissues. T3, like T4, is also highly protein-bound, but it is the free forms of T3 and T4 that are biologically active.

Although T3 is an important thyroid hormone, it is of little use in the diagnosis of feline hyperthyroidism; therefore, veterinarians rarely order this test.
If the thyroid gland produces too much T4, the rate of the cat’s body functions will increase and cause symptoms associated with hyperthyroidism such as weight loss, increased appetite, increased heart rate, anxiety, and vomiting. The most common cause of hyperthyroidism in cats is a benign thyroid adenoma but some cats will develop thyroid cancer or carcinoma. The effect of these conditions on thyroid hormone production can be detected by measuring the total T4 (includes both the protein-bound and free portions of T4) or the free T4 (measures just the free or unbound portion of T4).

How is it used?
Total T4 and free T4 are two separate tests that can help the veterinarian evaluate thyroid function. The total T4 test has been used for many years as a diagnostic test for humans, as well as dogs and cats. It is a very useful test and is the main test used to confirm suspected hyperthyroidism in cats.

What does the test result mean?
In general, a high total or free T4 result indicates an overactive thyroid gland (hyperthyroidism). The test results alone are not diagnostic but must be interpreted together with your cat’s clinical signs, symptoms, and physical examination findings.  

Since free T4 is the active form of thyroxine, it could be thought to be a more accurate reflection of thyroid hormone function than total T4. Indeed, the free T4 test is a more sensitive diagnostic test than is the T4 test, i.e., the free T4 test will be diagnostic in 98.5% of hyperthyroid cats whereas the total T4 test will be diagnostic in 91% of cats with the disease (See Figures 2 and 3). However, many cats suffering from other illnesses NOT associated with hyperthyroidism will have false-positive results with the free T4 test (Figure 3). For that reason, the total T4 test remains the diagnostic test of choice for cats with suspected hyperthyroidism because we almost never see false-positive results with the total T4 test.

Figure 2
Serum T4 results in 917 cats with hyperthyroidism, 221 cats with nonthyroidal disease (sick cats without hyperthyroidism), and 172 normal cats. Data are plotted as box plots, where the T‑bars represent the main body of data and the box represents the middle half of the data. The horizontal bar in the box represents the median. Outlying data points are represented by open circles. The shaded area indicates the reference range. Notice that none of the cats with nonthyroid illness have a high T4 value. From: Peterson ME, Melián C, Nichols CE: Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. Journal of the American Veterinary Medical Association. 218: 529-536, 2001.
Figure 3
Serum free T4 results in 917 cats with hyperthyroidism, 221 cats with nonthyroidal disease (sick cats without hyperthyroidism), and 172 normal cats. Notice that many of the cats with nonthyroid illness have a high T4 value even though they are not hyperthyroid (false-positive result).