Thyroid Panels: Predicting Breedability vs. Diagnosing Disease

For those who are GDCA (or affiliate) members, a short note on this topic is presented in the next upcoming (1st, 2004) Quarterly Bulletin. The below offers a similar (but very informal!) explanation of why, if you as a breeder are interested in the breedaibility of your Danes as to endocrine health, it is to your benefit to submit thyroid panels thru an approved laboratory for OFA analysis, and not simply use your vet's usual referral lab, some independent lab, or even the labs used by OFA without getting the OFA analysis. This article is to help breeders understand how to select the appropriate lab work, it is not a technical article on thyroid function or thyroid panels. For that, visit any number of technical sites or simply visit with a specialty veterinarian. 

WHY IS THE OFA PANEL BETTER? 
What's "wrong" with just getting a T4 done by your veterinarian, or letting someone who advertises analyze your dog's thyroid results? What's the difference and why do you get offered different things to analyze and end up with differing results? I think the heart of the matter here is critical, as there IS a "big difference" in who and how a blood sample is analyzed for thyroid function and it is one that very important to understand. But unfortunately it's not widely discussed so is very often misunderstood and people just end up looking at a bunch of numbers & get all confused.

Here are the basics and a simple explanation. OFA is judging the dog's thyroid results based on the dog's suitability for breeding. They have strict guidelines to define the profile in various ways beyond "normal" and "abnormal." That is their function: OFA provides a BREED SCREENING TOOL. Your vet's referral lab, "specialty labs," and even labs like MSU/UCDavis, typically are sent a large number of samples from vets with sick dogs that have clinical symptoms that might mean thyroid disease. So these labs have set their protocols and reading procedures up to look for patterns that will tell a vet if the sick dog in his clinic is sick because of thyroid disease or not. So what then typically happens is the lab then reads all abnormals that are not actually the profile of a specific disease as "normal" (ignoring small alterations), or at least as "not consistent with thyroid disease" and such labs give NO interpretation as to the likelihood that dog will pass on disease. 

This answers the vet's question of: "have I for sure found the answer to why this dog is sick?" This is NOT the question that the breeder of a young, healthy dog has. The OFA panel _can_ answer this question that you as a breeder want answered when sending in the blood on your normal, healthy animal: "Does my animal have a thyroid profile that demonstrates normal values indicating the dog is, in this, a good breeding candidate?" 

THAT answer is provided by OFA, as THOSE are the standards that OFA judges by. They are particular in what labs they use, making sure each one meets their standards. And they test specifically and exactly for the thyroid values than CAN answer the question a breeder has on a young healthy animal. And they read the results with the breeder's question in mind. 

The OFA panel can also answer questions of active disease in a sick animal, confirming thyroid disease is the underlying reason, but that is not its function per se. The OFA panel is set up (by the acknowledged experts in this field) to tell you as a breeder if your dog's values are not completely normal and to indicate to you if there is any reason to be cautious in breeding the animal at this time. If just some the dog's values are off, say just one is, then the report is therefore "inconclusive" at this time, and the dog's breeding status is uncertain. Retesting in 3-6 mo. (as recommended) typically clears up any confusion. Either you then see a return to normal, as the "off" value was simply from some transitory "blip," or you see a pattern of abnormal values that then tell you this animal's breedability is in question as heritable thyroid disease is indicated by its lab results.

OFA is not defining clinical disease in the dogs with this screening, it's trying to define the breeding value of the dog as to the likelihood they will (even in the future) contract a hereditary disease of the thyroid. IF the dog isn't clearly diseased, then it gets an equivocal, which is NOT a fail, and the owner is advised to retest in 3-6 mo. I do NOT know any a single case where the owner followed thru with these instructions that the 2d test did not do just that for them. Most times the second test is normal when a small anomaly was present on the first test. So don't be afraid to retest~! This system Dr. Nachreiner, the acknowledged leader in this field, set up and I firmly believe the protocols are as good as can be. (For better we need a gene test.)

HOW DOES OFA RATE MY DOG'S THYROID?
OFA doesn't rate a dog on just T4 or on even a "bunch" of thyroid values (as some labs do), as so many then end in inaccurate values or inconclusive tests. 

OFA rates a dog on the three values:
FT4D: the gold standard for accurate thyroid activity detection.
cTSH: the gold standard for measuring the stimulating hormone.
TgAA: the most accurate single assay for pathological autoantibody production.

It's important to use the right measures and standards on any test. With something as dynamic as thyroid function, it is *critical* to have exacting protocols & measure the right values. And even *if* all this was the same, the interpretation still can be different. WHY? Different questions get different answers using the same profile. That's simply how lab work functions. You have to ask the right questions to properly interpret the data. So for what you and I want, as breeders, OFA is asking the right questions. For what the majority of people with sick pets want to know, the referral lab is answering the question the vet asked for. But it won't give us the answers we as breeders need.

A SHORT EXPLANATION OF THYROID FUNCTION. 
I keep saying thyroid function is dynamic. Anyone can go to a number of expert sites and get a long and medically accurate portrayal of the function and feedback loops in Endocrinology. So I'm just going to offer a "snapshot" here of what's going on and "what's going wrong" typically with dogs who have heritable thyroid disease (i.e. autoimmune thyroiditis). (Skip to the end if you don't care about the details of function.) In a dog with a healthy thyroid, if the thyroid activity falls, (e.g. T4/T3 values, to be abbreviated as FT4D in this explanation), there is a surge in the hormone that stimulates the thyroid (TSH). TSH goes up, then FT4D goes up, so the TSH then falls. It's dynamic and flexible, and it involves a negative feedback loop: as the FT4D value rises, the TSH value falls. 

When a dog has heritable hypothyroidism and is young, he has auto antibodies to his own thyroid function. The thyroid is slowly killed off by this dysfunction of the dog's immune system. SO for a while the feedback system still works, but it has to work harder and harder as time goes on and less and less thyroid tissue is left undisturbed and working. So you start to see certain values go haywire. Auto antibodies are found at measurably significant levels & in very specific forms. And the values for thyroid function, such as FT4D, start to be lower and lower. Maybe in the beginning they are just "low normal" or maybe some are normal range and others are not.

Maybe on one panel there is a surge in TgAA and another there is a low FT4D or just a high TSH. This happens as the antibodies are actively destroying thyroid tissue. These sorts of patterns suggest heritable autoimmune hypothyroidism. This shows a pattern where the dog's system in working overtime to get thyroid hormone out into the body (High TSH), but there is little response from the thyroid (low FT4D) all because there are self-destructive antibodies present (positive TgAA). Meaning, essentially that the immune system is slowly destroying the dog's thyroid, so the TSH goes up as it is "shouting" (very loud): "Get some more T4/T3 out in the system!" Which the dogs thyroid cannot do, as there is "no answer", because there can be no real good rise in the FT4D, even though TSH is "screaming" now "PLEASE!". Eventually you have the whole pattern of a hypothyroid dog, with a high TSH, a low FT4D, and a positive TgAA. But it takes some time for this to develop, as all that shows up only when enough of the thyroid is gone. (Eventually the positive TgAA actually goes away, as no thyroid tissue left means no more stimulation of thyroid-killing antibodies.) 

WHAT OFA CAN DO FOR YOU.
When the dog has all three values as stated above: high TSH, low FT4D, and positive TgAA, then the dog is defined by OFA (and anyone really) as having positive Autoimmune thyroiditis. If the dog's got high TSH and TgAA, but normal FT4D, it still has hereditary hypothyroidism, but the dog is right now compensating (TSH has screamed loud enough and the FT4D can still hear and answer the call). If the dog has a negative TgAA but high TSH and low FT4D, it's usually older and gotten to the point it's killed its own thyroid. (No need for antibodies when no active thyroid tissue left, remember?)

But OFA doesn't stop here, and doesn't even stop in defining thyroid diseases, it ALSO defines a normal profile for the thyroid. That's when the TSH stays low, the FT4D stays up (high) & humming along, and there isn't a TgAA level that make you suspicious the thyroid's being destroyed by antibodies. And for THAT set of lab values, OFA gives a certification for normal thyroid. IF any one value is off, fairly OFA gives you your money back and tells you to retest in 3-6 months. That way the dog isn't judge unfairly as a (poor) breeding candidate just on a "snapshot" of his thyroid function. One single value being "on" or "off" isn't much information. That's why it's a total waste of money for breeders to check T4 in their dogs. That being normal is meaningless as a breed screen. Arguably checking TgAA every year might be the only useful single test, but it's not as good as checking to see "the big three" (FT4D, TSH and TgAA) are all what they should be. See here for the details: http://www.offa.org/thygrade.html


When you have some values "off" and some "on"--that's not as much a conflicting picture (if you understand how this test and the thyroid basically work), but it's not a "wide" enough view of what's happening with the dog's thyroid function is all. The idea here is that these single panels are just a "snapshot" of an organ that is involved in dynamic function. So any other illness or even strong physiologic stressor can make one panel be off. However, more than one panel will typically show the true pattern of thyroid function in a dog. That pattern can be one of many diseases, starting or ending with the thyroid, or it can be totally normal function. If there is not a clear-cut pattern in how the values are off (as OFA outlines at the above url), then you can certainly say that the lab values are not totally normal, but the reason for it being "off" is not yet defined. However, practically speaking, a repeat OFA thyroid panel in 3-6 months will show you/your vet what the pattern is as to the dog's thyroid as well as tell you as a breeder whether this dog is at high risk for producing thyroid disease in it's offspring. That's the beauty of submitting the lab work to OFA: they answer this last question that the breeder really needs to know. 

CONCLUSIONS.
I hope this have been helpful. Again, I caution this is a non-technical article and details have been ignored for the safe of clarity. However, the take home message, if you are breeding dogs, is have your healthy adult dogs get an OFA screening panel, and don't waste your money on these lab panels that are set up to screen disease in sick pets. 

For more, see the OFA section on thyroid; many links there:
http://www.offa.org/thyinfo.html

Here are some frequently asked questions answered:

Where can I find the OFA thyroid form and directions for the test? 
The forms & instructions can be downloaded from the OFA website. You as the owner need to fill out the top portion, your attending veterinarian examines the dog and draws blood, while attesting to the dog's health, and the serum is sent to the laboratory where it's processed and the results sent to OFA and returned to you vet as well. Be sure to include the paperwork and fees for processing with the blood (serum) sample.

Which labs will OFA accept results from?
This list of labs and the tests that must be done by them are also on the form for the OFA thyroid and at the OFA website. There are several labs in various parts of the country and the sample is simply sent in the mail from your vet to a nearby lab. (There are even two in Canada.) MSU, Cornell, UCDavis, UMinn and TxA&M provide testing, but you cannot just send it off to your vet's "regular" lab necessarily and have to include the OFA paperwork for such as MSU to provide to OFA the results. Note that OFA and your vet will both get the results back, so you will see them too.

What is the minimum age for certification?
12 months is the minimum age allowed, but a good time to start would be 2-3 years when doing the OFA hip exam anyway. Your local vet can usually do both. 

How long are results "good/valid"?
OFA has suggested, in accordance with expert guidelines, that dogs be checked regularly as an adult. Annual testing from 2-4 years is ideal. Biennial thyroid testing after that will suffice. 

What can interfere with testing? (drugs, heat cycle, etc.) and when should bitches be tested? 
Illness, certain drugs and even the oestrous cycle can potentially interfere with thyroid testing. This is another reason to simply schedule that first OFA thyroid when you are planning an X-ray for OFA hips. Dogs undergoing thyroid testing should be in good. Bitches should be in anestrous ideally. Any medications should be discussed with the vet prior to testing.

What happens if my result is equivocal?
Equivocal is not a "fail" nor does it mean the dog has thyroid disease. It means the results of the test were
inconclusive and should be repeated in 3-6 months. Upon repeat of the testing, most dogs will then receive a clear "pass" or "fail." The dog will STILL receive its CHIC certification right away.

If you have any more questions, please feel free to contact me personally or check with the other links provided at this website for more information.

JP Yousha
Chmn., Health & Welfare Committee
Great Dane Club of America
http://www.gdca.org/healthandwelfare.htm
danehealth@gdca.org
432-684-8940 (CT-USA)

Permission to reprint as submitted for educational purposes is given. 
Submitted by JP Yousha, Chair, H&W Committee, GDCA 2004.

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