Sponsored by an educational grant from IDEXX Laboratories, Inc. Current concepts on diagnosing and managing thyroid disease in dogs & cats Canine Hypothyroidism The thyroid, the largest endocrine organ, influences the function of almost every Primary hypothyroidism is due to impaired function and secretion of organ in the body. The thyroid produces the thyroid hormones. Most dogs have acquired hypothyroidism that is thyroxine (T4) and triiodothyronine (T3), either lymphocytic thyroiditis or idiopathic thyroid atrophy. It is most which regulate the rate of metabolism commonly diagnosed in middle-aged dogs and often affects mid- to and affect growth and rate of function of large-size breeds. Clinical signs vary, and because the clinical signs of many other body systems. Dogs and cats both suffer from dysfunction of this hypothyroidism can be indistinguishable from other diseases, it is important gland. The onset of thyroid commonly overdiagnosed. Age, breed, and systemic illness all affect disease is often insidious in pets, thyroid hormone concentrations. occurring over months to years and may not be clinically apparent from Dr. Robertson: The most common clinical signs in dogs with hypothyroidism the history or the physical examination. are dermatologic conditions and signs secondary to a decreased metabolic rate. What are some of the uncommon presentations you see? Jane Robertson, DVM, Diplomate ACVIM Head of Internal Medicine Dr. Nelson: Dogs with neurologic signs, including seizures, neuromuscular IDEXX Laboratories, Inc. disorders, and peripheral neuropathies, are recognized. These manifestations West Sacramento, CA are related to the profound hyperlipidemia (hypertriglyceridemia) that these dogs have. When the triglyceride levels are >1000 mg/dL, you may have gastrointestinal signs that mimic pancreatitis. Richard Nelson, DVM, Diplomate ACVIM Dr. Scott-Moncrieff: Cranial nerve changes are not common, but they are an Professor of Internal Medicine important manifestation of hypothyroidism and reversible with appropriate School of Veterinary Medicine treatment. University of California, Davis, CA Dr. Kintzer: There have been reports Canine Hypothyroidism of cerebrovascular accidents as well. Clinical Signs J. Catharine Scott-Moncrieff, Clinical signs develop slowly and are VetMB, MS, MA, Diplomate Dr Robertson: What are the typical ACVIM (SAIM) & DECVIM (CA) progressive. findings you would expect on a Professor of Internal Medicine Director of International Programs minimum database? Common School of Veterinary Medicine Lethargy, inactivity, weight gain, cold Purdue University intolerance, hair loss or excessive West Lafayette, IN Dr. Scott-Moncrieff: The classic shedding, lack of hair regrowth following changes on the hemogram are a mild clipping, dry or lusterless hair coat, Peter Kintzer, DVM, normocytic, normochromic, non- excessive scaling, hyperpigmentation, Diplomate ACVIM* regenerative anemia. The classic recurrent skin/ear infection Internist Animal Medical Center changes in the biochemical profile Uncommon of New England include very mild increases in liver Generalized weakness, incoordination, Nashua, NH cardiovascular abnormalities, facial enzymes and changes in the * currently internal medicine consultant, paralysis, seizures, neuropathies, infertility cholesterol and triglyceride values. IDEXX Laboratories, Inc. IDEXX Laboratories, Inc., advertorial / NAVC Clinician’s Brief / November 2010 1 Sponsored by an educational grant from IDEXX Laboratories, Inc. Thyroid Tests Available The large majority (~ 75%) of hypothyroid dogs have increased cholesterol values, and an even higher number have increased triglyceride values. Total thyroxine T4 or TT4 Total triiodothyronine T or TT 3 3 Testing for Hypothyroidism Free thyroxine fT 4 Dr. Robertson: Confusion exists around the value of the various available Thyroid-stimulating hormone TSH diagnostic tests for hypothyroidism and the best protocol for ruling out or Thyroglobulin autoantibody TgAA diagnosing this condition. Total T4 can be performed in-house or at a T4 autoantibody T4AA reference laboratory. All other thyroid testing is offered only at reference T3 autoantibody T3AA laboratories. Let’s begin the discussion with the value of screening for hypothyroidism using the total T4. Dr. Scott-Moncrieff: Total T4 is a great screening test to rule out this disease. You need to look at it in the context of clinical signs. If a dog isn’t gaining weight, doesn’t have any other clinical signs, and the total T4 is above 2 mcg/dL, I don’t pursue diagnosing hypothyroidism any further. Dr. Nelson: Total T4 is a good screening test for normal dogs, but the problem is that most variables affecting the thyroid gland cause the T4 to go down for various and sundry reasons, yet the thyroid gland is normal. It’s a protective What if the total T is increased 4 mechanism and very little causes it to go up. If you get a low T , it becomes a in a dog not receiving thyroid 4 question of, is the animal hypothyroid or is something suppressing thyroid supplementation? secretion and causing the low numbers? The normal reference interval for any test comprises results from 95% of the population, so by definition 5% of normal Dr. Kintzer: I do a total T4, using the SNAP Total T4 Test, in my practice first. dogs will have a T4 result that falls outside (A new,improved version of this test will be released in early 2011.) If a dog with of the normal reference interval. True clinical signs has a total T4 above 2 mcg/dL but is still in the reference range, hyperthyroidism is rare and may be seen in I start looking for something else that is causing the clinical signs. I often like some cases of thyroid carcinoma and the efficiency of running the test in-house because I don't have to play phone adenoma. If the T4 is increased and the dog is not on a supplement, look for clinical tag with the client.' signs of weight loss, tachycardia, and a palpable mass in the cervical region. Dr. Robertson: To summarize, we all agree that if the total T is well within Consider running a fT4 and T4AA. A 4 detectable TSH concentration rules out the reference interval, hypothyroidism is extremely unlikely. However, hyperthyroidism. if the T4 is low or at the low end of the reference interval, what additional diagnostic steps do you take to establish whether a dog is hypothyroid or not? Dr. Scott-Moncrieff: First, you need to look at the animal and its signalment. We know that total T4 is highest at 6 months to a year of age. Over the lifetime of that animal, it is going to decrease by 60%; we should probably have age- and breed-specific reference ranges. Dr. Kintzer: The medication history is important too. Is it an epileptic and getting phenobarbital? Did it just finish a course of trimethoprim sulfadiazine/ sulfamethoxazole for a skin infection? Or is it on an immunosuppressive dose of corticosteroids? We have to consider all of those things. Dr. Scott-Moncrieff: But if hypothyroidism is still on your differential list and the patient has clinical signs of hypothyroidism, further testing is indicated. If the owner’s resources allow, I prefer to go from a screening 2 NAVC Clinician’s Brief / November 2010 / IDEXX Laboratories, Inc., advertorial test to a thyroid panel and look at everything. If not, I’m likely to start off by adding a TSH and fT4. Dr. Kintzer: In the hospital where I work, I run into more economic considerations, so I usually just perform the TSH and the fT4 and add additional thyroid tests if necessary. Dr. Robertson: Let’s talk about the individual components of the thyroid panel. How does the fT4 differ from the total T4? Dr. Nelson: The fT4 measures the nonprotein-bound form of circulating thyroxine, which is available to tissues. The majority of T4 is protein-bound and is a reservoir. fT4 is the physiologically active component that, in theory, should give you a better reading of thyroid gland function than the total T4. The problem is that a lot of the work done on fT4 looked at human radioimmunoassay tests (RIAs). The human RIAs just don’t work well in the dog. For a long time, equilibrium dialysis was considered the “gold standard” procedure for the measurement of fT , but the test seems to 4 Total T4 is a great screening test have changed since it was first evaluated in the 1990s and other, newer to rule out hypothyroidism. You fT4 assays may perform just as well or better. need to look at the total T4 in the Dr. Kintzer: Regardless of the testing methodology, we need to remember context of clinical signs. If a dog doesn’t have any clinical signs that although the fT4 is generally a better test than total T4, it’s still not a perfect test to determine if a patient is hypothyroid because it can be affected of hypothyroidism, and by nonthyroidal illness as well. the total T4 is above 2 mcg/dL, I don’t pursue diagnosis any Dr. Scott-Moncrieff: I think a fT is better than a total T , but the fT is not 4 4 4 further. as good as the 1990's papers made it look. Some people believe the fT4 is independent of euthyroid sick syndrome, but if the animal is sick enough, the fT4 can be low as well. Another important concept is that in an adult dog that’s not systemically ill, the lower the total T4 or the fT4, the more likely it is that the animal is truly hypothyroid. Euthyroid Sick Syndrome Dr. Robertson: So we’re looking at additive information. The fT4 is not a Euthyroid sick syndrome (ESS) refers substitute for the total T4. The total T4 is a good screening test for suspected to a condition in which dogs have a nonthyroidal illness (NTI) that suppresses cases. If the total T4 is low, the clinician should consider performing additional diagnostic tests to help confirm or rule out hypothyroidism.