Thyroid Glands in Horses
- Jul 1, 1999
A properly functioning thyroid gland is highly important to a horse's good health. That much is easy. From there it gets more difficult and complex. Knowing when the thyroid gland is in a state of dysfunction is not easy to determine.
If the thyroid gland is removed, animals show several signs, including a dull, coarse hair coat that fails to shed at the appropriate time.
The problem or issue before the house, at least one researcher believes, is that the thyroid gland, in a number of instances, might be innocent of any wrongdoing and that some treatment protocols are creating problems they are seeking to remedy. That researcher is Nathaniel T. Messer IV, DVM, of the University of Missouri in Columbia. At the December, 1998, AAEP meeting in Baltimore, Messer, who conducted a good deal of research on the thyroid gland, also presented a paper that detailed the results of a study at two central Kentucky Thoroughbred farms involving low hormone levels in mares and foals.
Messer summarized the complexity of the thyroid debate with this opening statement in his presentation at Baltimore:
"There is a wide spectrum of equine clinicians with varying beliefs about thyroid disease, ranging from those who believe thyroid disease is common and often diagnose it in horses who are infertile, have laminitis, or race poorly, to those who do not even believe it exists.
"In adult horses, thyroid dysfunction is generally felt to be uncommon, and while it has been associated with a variety of clinical signs, a definitive diagnosis is often difficult. One of the reasons for this is that many endogenous and exogenous factors can affect thyroid function and sometimes test results. Serum levels of thyroid hormones vary over a wide range, and low baseline levels may be misleading, which may result in many euthyroid (normal) horses being diagnosed as hypothyroid.
"Despite the difficulty in definitively diagnosing a thyroid dysfunction in adult horses, it is estimated that over $750,000 worth of thyroid supplement is sold for use in horses annually."
More on Messer's Baltimore presentation later. First, let's take a look at what he and other researchers have learned about the thyroid gland.
Part of the difficulty involved in diagnosis and treatment of a thyroid problem, or alleged problem, stems from the fact that there currently are no totally reliable tests that can provide a definitive answer in horses. Such tests are available for people, and researchers are on track to develop them for horses; but as of now, they simply don t exist.
This isn t to say that horses aren t being tested for thyroid abnormality. They are. But Messer is convinced that the routine tests might very well provide incorrect information as to the actual functioning, or lack of same, of the thyroid gland. As a result, he is sure, a large number of horses which might not have thyroid problems are being treated with thyroid hormones. Treating a horse with hormones when its thyroid gland is normal can serve to create the very problems that the hormones allegedly are correcting.
All vertebrates have a thyroid gland. In mammals, it is located just behind the larynx and adjacent to the trachea. The thyroid gland has two lobes, one on either side of the trachea. In horses and ruminants, the two lobes are connected by a fibrous isthmus.
The hormones produced by the thyroid gland are the only ones in the body that contain iodine. The main secretory product of the normal thyroid gland is thyroxine (T4). The thyroid also secretes triiodothyronine (T3) and other non-iodine metabolites. A significant amount of triiodothyronine is derived from thyroxine. In that scenario, thyroxine acts as a prohormone and is degraded enzymatically to triiodothyronine in peripheral tissues. Triiodothyronine is three to five times more potent than thyroxine.
Hormones secreted by the thyroid gland serve many functions in the body. They act as growth regulators and are involved with cell differentiation and oxidative metabolism.
However, the primary function of thyroid hormones, says Messer, is the maintenance of the metabolic rate. "To effect their actions, thyroid hormones bind to nuclear receptors and are capable of acting directly on the genome to initiate transcription and translation. Major sites of hormone action, such as the cell membrane, mitochondrion, ribosome, and nucleus, are similar in both the adult horse and young foal."
Both the pituitary gland, which is located at the base of the brain, and the hypothalamus, which is located in the brain and attached to the pituitary, are involved in regulating thyroid gland function.
Messer explains the interaction this way: "Thyroid hormone secretion is controlled by thyrotropin (TSH, the acronym for thyroid stimulating hormone, which is what thyrotropin does). Thyrotropin is released from the anterior pituitary gland under the effect of thyrotropin releasing hormone (TRH) from the hypothalamus.
Any or all three thyroid gland, pituitary, and hypothalamus might be implicated when a problem occurs.
"Primary hypothyroidism," Messer explains, "is due to inadequate production of thyroxine or triiodothyronine from the thyroid gland. Secondary hypothyroidism results from a deficiency of thyrotropin from the anterior pituitary gland. Tertiary hypothyroidism results when insufficient quantities of thyrotropin releasing hormone are produced by the hypothalamus."
However and it is a major however what appears to be hypothyroidism due to dysfunction of the thyroid gland might, in reality, be inadequate conversion and utilization of thyroxine and triiodothyronine as the result of non-thyroidal factors.
In horses, the conversion and utilization might be stymied by such factors as stress, high energy diets, high protein diets, and diets high in zinc and copper. In addition, says Messer, "based on the findings of current studies, it would appear that such factors as glucocorticoid administration, food deprivation, and ingestion of endophyte-infected fescue grass also may result in low plasma levels of thyroxine and triiodothyronine in euthyroid horses (those having normal thyroid function)."
In experiments where the thyroid gland was removed from horses, Messer said, the animals failed to grow, were sensitive to cold, had dull, coarse coats that failed to shed at the appropriate time, were docile and lethargic, had high blood cholesterol concentrations, decreased rectal temperatures, and anemia.
Research, Messer says, has changed the time-honored perception of the appearance of a horse suffering from hypothyroidism. "There is a big discrepancy between what hypothyroidism looks like experimentally and what people think it looks like in a clinical setting. The typical hypothyroid horse in most people s minds both owners and veterinarians is the horse that has a fat, cresty neck and has laminitis. That horse has, over the years, for some reason, become everybody s idea of a hypothyroid horse. Some of those horses do have a low thyroid level, but very few of them have been worked up and proven to have thyroid glands that are abnormal. All they have are low thyroid hormone levels, and many of those horses, if you really look at their endocrine system, probably have pituitary disease or some other endocrine system abnormality."
Hypothyroidism, when it occurs in foals, can bring about irreversible damage.
Insufficient iodine reduces the ability of the thyroid gland to make thyroid hormone. With reduced circulating thyroid hormone levels, the pituitary gland is stimulated to secrete more thyroid stimulating hormone which, in turn, acts as a stimulus for hyperplasia (the abnormal multiplication or increase in the number of normal cells in normal arrangement in a tissue) and goiter (enlarged thyroid gland).
Goiter caused by iodine deficiency is most common in newborn pigs, lambs, calves, and foals in iodine-deficient territories. When a young animal has goiter, the thyroid lobes usually are at least twice normal size, soft, and dark red. In severe cases, there is an accompanying lack of hair. The neck usually is grossly enlarged, and the skin and other tissue might be thickened, flabby, and show signs of edema.
In mildly affected animals, treatment with iodized salt might solve the problem, but many young animals so afflicted will die before or soon after birth. It s a case where an ounce of prevention is worth a pound of cure. If one has horses in an iodine-deficient area, it is a must to make iodized salt available.
Certain plants can produce goiter when ingested in sufficient amounts, especially in the absence of adequate iodine intake. Soybeans are most notable, but cabbage, rape, kale, and turnips all contain less potent goitrogen. There is good news here, especially for horsemen feeding soybean meal as part of the diet. The normal processing of soybeans destroys the goitrogenic substance in these plants.
All of the goitrogenic substances act by interfering with production of thyroid hormone. As is the case in iodine deficiency, the pituitary gland responds to the reduced circulating thyroid hormone levels by increasing its secretion of thyroid stimulating hormone, which can result in thyroid gland enlargement. Normally, goiter is not a major cause for concern in adult horses.
Respiratory distress and gastric ulcers also have been reported in association with hypothyroidism in foals.
Hypothyroidism in foals can be treated with thyroid hormone supplements, but in many cases by the time the problem has been diagnosed, permanent damage already has been done. "You re not going to be able to correct collapsed tarsal or carpal bones," says Messer.
With an understanding established of how the thyroid gland functions and what happens when it doesn t work properly, the question is this: Is thyroid dysfunction prevalent among horses?
Is There A Problem?
Messer is clearcut in his viewpoint: "In horses, thyroid dysfunction appears to be an uncommon problem that is difficult to definitively diagnose by use of the currently available tests of thyroid function."
Yet, he acknowledges, a large number of horses, including many Thoroughbred broodmares in Kentucky, are being treated every day for deficiency of thyroid hormones. A major part of the problem, he says, stems from the fact that the only tests available commercially often do not provide a clear picture of what is occurring with the thyroid gland because of outside or non-thyroid factors.
However, there is a bright light at the end of the tunnel. A TSH assay procedure has been developed in the laboratory and, hopefully, will be available on a commercial basis in the near future. The TSH assay approach, says Messer, will help lead the way to accurate diagnoses, as long as the assay is specific for equines.
At the moment, however, diagnosis for the practitioner in the field often is difficult. The thyroid gland, Messer said, might be working just fine and could be capable of producing adequate levels of hormones. However, the levels within the horse s system might be affected, for example, by ingestion of endophyte-infected fescue grass or the injection of phenylbutazone.
Something as basic as food deprivation can have an effect on the amount of thyroid hormones found in the horse s system. Thus, if a horse goes off feed and is tested for hormone levels in the blood plasma, the hormonal levels might very well be low, even though the thyroid gland is functioning normally. The simple fact that the horse is not ingesting an adequate amount of food could be the factor causing low thyroid hormone levels.
"We must be able to measure thyroid stimulating hormone (TSH)," Messer said.
When TSH is measured, he points out, the hypothyroid horse will have high levels of TSH because the pituitary gland is making a strong attempt to communicate a need for hormone production to the thyroid gland. Conversely, if the thyroid gland is functioning normally, the TSH levels are either normal or low.
Involved in this scenario is the feedback mechanism. Basically, the feedback mechanism works like this: When the thyroid gland is producing enough hormones, the blood going back to the brain carries the message to the pituitary gland that there is enough product out there and it can slow down on its production of TSH. When the hormonal levels are low, the message carried back to the pituitary is for increased production. Then the pituitary sends out more TSH which, in turn, stimulates the thyroid gland to produce additional hormones.
It is here that a problem can evolve in the treatment with thyroid supplements of horses that have a normally functioning thyroid gland. If an incorrect diagnosis is made based on low blood plasma levels of thyroid hormones which, in fact, have resulted from non-thyroidal factors and thyroid hormone supplementation is administered, the pituitary gland is going to get the wrong message.
The message carried to it is that there is an abundance of thyroid hormones in the system. Thus, the pituitary gland will shut down its production of TSH, which in turn causes the thyroid gland to shut down production of its hormones.
Under such circumstances, says Messer, "If we put thyroid hormones in there, all we re doing is shutting down the thyroid gland. Treatment could cause the problem we re treating and make the animal dependent on thyroid hormone supplementation. If you have a normal thyroid gland, but the hormones it is producing are being tied up, destroyed, or used up by other factors, and you start administering thyroid hormones, you are going to suppress the normal thyroid gland."
Why is Messer convinced that very few horses have an abnormal thyroid gland?
"The bottom line," he said, "is that if you go back and review the thyroid glands examined at post-mortems, you will find that there are very few horses that have abnormal thyroid glands. In dogs and people, abnormal thyroid glands appear in a fair number of instances.
"In the horse, we see occasional tumors, occasional goiters, but we see very few horses that have abnormal thyroid glands. That leads me to believe that there are very few horses that have true hypothyroidism.
"I clearly admit that I don t know for sure, but I am fairly confident that in most horses that have low thyroid hormone levels, if you corrected something in their environment or took something away with which they re being treated, that they wouldn t have that problem."
As mentioned above, administering phenylbutazone can have an effect on thyroid levels in the blood.
"One of the most scientifically done papers," Messer said, "was published in the mid-1970s. The researcher looked at muscle problems in racehorses and made the correlation between low thyroid levels and horses developing muscle problems. From that time forward, horses with muscle problems are suspected of being hypothyroid and are put on thyroid hormone supplements."
The problem with the study, he said, is that at that point in time, no one knew that phenylbutazone had a negative effect on thyroid hormone levels in the horse. That also was an era when there were fewer restrictions on the use of phenylbutazone and its administration might have been more prevalent than it is today.
So, he concludes, perhaps a great many of the horses included in that research were being administered phenylbutazone, and it might very well have been that drug, rather than exercise and/or thyroid gland problems, that affected thyroid hormone levels.
Until better testing procedures make their appearance beyond the research laboratories, the horse owner and the veterinarian are going to have to do an even better job in looking at a horse s history before making the diagnosis that a horse has thyroid gland problems, Messer believes.
Messer s report at the Baltimore AAEP convention was based on a study that was conducted in 1996 on two large Thoroughbred farms in Central Kentucky to measure thyroid hormone levels in mares and their newborn foals at the time of parturition. The study produced some interesting findings, but, above all, it underscored the difficulty involved in correctly identifying thyroid dysfunction in the horse.
The two farms involved in the study were selected because the management of the horses at each respective farm varied at the time of parturition. Messer identified the two farms only as Farm A and Farm B.
One of the differences between the two farms involved the pastures. The pastures on Farm A contained endophyte-infected fescue while the pastures on Farm B were nearly free of any endophyte-infected grass.
Before the study was begun, baseline serum levels of thyroxine (T4) were determined in mares on both farms at the time of breeding, and, based on those results, mares were supplemented on a daily basis with thyroid hormone. That supplementation, Messer said, has become something of a common practice on many breeding farms in Central Kentucky.
Mares on Farm A with endophyte-infected fescue were removed from the infected pasture approximately 30 days before foaling and treated with domperidone, the drug developed at Clemson University to prevent or treat fescue toxicosis. (Domperidone is available as an experimental drug and is available to veterinarians only through the Clemson University laboratory. Clemson is in the process of seeking general approval for domperidone from the FDA. That approval, say university officials, is expected by the end of 1999. After approval, it will be more generally available as a prescription drug.)
Mares on Farm B were allowed daily access to pasture and were not treated with domperidone.
Approximately 30% of the mares on Farm A and 40% of the mares on Farm B were estimated to be on some form of thyroid hormone supplementation throughout their pregnancy.
Within 25 hours after foaling, blood was drawn from the mare and the foal. There were 104 mare-foals pairs involved 52 on each farm.
Samples were analyzed for levels of thyroxine (T4), triiodothyronine (T3), reverse-triiodothyronine (rT3), and thyrotropin (e-TSH).
"The number of mares and foals on both farms with thyroid hormone levels above or below the normal reference range was remarkably high," Messer reported. "Overall, 69.6% of the mares and 83.3% of the foals had T4 levels below normal reference ranges. Although the mares were not considered to be low for T3, 40% of the foals had T3 levels below the normal reference range for day-old foals."
Sixty percent of the mares had rT3 levels above the normal reference range.
(In another part of the report, Messer explained that increases in rT3 in adult horses have been recognized in association with dexamethasone administration, food deprivation, and in stressed neonatal foals. He explained that extrathyroid illness also is called euthyroid sick syndrome. This syndrome, he said, represents an adaptive mechanism to decrease the metabolic rate during periods of illness and stress and when the thyroid gland is considered to be normal. More study is needed, he said, to determine why the mares in the study had low T4, normal T3, and high rT3.)
"Overall, there was no significant difference between mare e-TSH (thyrotropin) levels and foal e-TSH levels," reported Messer. "The percentages of mares and foals with e-TSH levels above the normal adult reference range on Farm A were 22% and 23%, respectively, whereas the percentages of mares and foals with e-TSH levels above the normal adult reference range on Farm B were 58% and 45%. The percent of elevated TSH levels was less than expected, considering the high percent of both mares and foals with low thyroid hormone levels.
"The percentage of foals with various types of conformational scores was similar between farms," he continued. "The percentage of foals in the various gestational age categories was similar for the two farms. No foals were classified as premature. The mean time to first suckling for the foals was 2.1 hours within a range of 0.2 to 6.5 hours.
"Even though there were several foals in our study with a variety of conformational abnormalities or deformities, we did not identify any foals with typical signs of congenital hypothyroidism-dysmaturity syndrome, despite having 83.3% of the foals with low T4 levels and 40% of the foals with low T3 levels."
One of the reasons more mares and foals had lower e-TSH levels on Farm A, Messer said, could be the result of ingesting endophyte-infected fescue. However, he added, it also could be the result of thyroid hormone supplementation, or even both.
Messer also outlined other factors, in addition to endophyte-infected fescue and thyroid hormone supplementation, that can have an effect on the level of thyroid hormones in the blood.
"The effect of late-term pregnancy on thyroid hormone levels in mares appears to be variable, with studies showing either no change or a decrease in thyroid hormones in late pregnancy. This is in contrast to what happens in humans, in which thyroid hormone levels increase in late pregnancy as a result of estrogen-induced increases in
thyroid-binding globulin and of stimulation of the thyroid gland by TSH-like activity of human chorionic gonadotropin, but it could be an explanation of the high number of mares with low T4 in this study.
"Two studies involving Thoroughbreds have shown that resting T4 levels were well below the normal range of values used by the respective laboratories of the investigators, leading to the conclusion by both investigators that measurement of T4 as an indication of thyroid function in the Thoroughbred is unreliable.
"It could be that Thoroughbred broodmares normally have thyroid hormone levels that are lower than the published reference range.
Nutrition As A Contributor
"Another factor which is not addressed in this study, but which affects thyroid hormone levels, is nutrition," said Messer. "It has been shown that short periods of food deprivation result in low thyroid hormone levels. Diet composition has been shown to affect the level of T4 in the serum of Thoroughbred horses. During pregnancy, a deficiency in energy intake can contribute to lower concentrations of thyroid hormones in maternal plasma during late gestation, which can result in a reduction in the fetal nutrient supply and in low thyroid hormone levels in the newborn."
A study concerning the effect of food deprivation on thyroid hormone levels was conducted earlier at the University of Missouri by Messer and associates. In the study, six healthy, mature horses (three geldings and three mares four to 16 years of age) of various breeds were housed in box stalls for one week prior to the beginning of, and for the duration of, the study. All horses were fed a diet of rolled oats and timothy hay. Water was provided.
Horses in Messer s study had not received any anti-inflammatory agents, hormonal medication, or other drugs for at least six months prior to the study. All horses were considered to have a thyroid gland that was functioning normally, with appropriate amounts of hormone circulating through the horse s system.
Blood samples were drawn from each of the horses to establish baseline hormonal levels; then food was withheld from the horses for four days. Blood samples were collected each day.
After collection of the samples on the fourth day, horses were fed the same diet as was fed before food deprivation. Blood samples were collected for 72 hours after reintroduction of feed.
When blood samples were evaluated and data examined, the underlying finding was that thyroid hormone levels in the test horses decreased by 50% over the four-day fasting period. In fact, there was a 50% decrease in triiodothyronine (T3) after only 24 hours of food deprivation.
When the horses were put back on feed, the thyroid hormone levels, generally speaking, returned to baseline status within several days.
That particular study underlines the problem in correctly diagnosing thyroid conditions without the equine TSH assay. If, for example, a veterinarian were examining a horse which was off feed and suspected of hypothyroidism, he or she might test for thyroid hormone levels. Based on the findings of the University of Missouri research, the off-feed horse is going to have low thyroid hormone levels even if it has a normally functioning thyroid gland.
Messer sums up the complexity of the diagnostics problem with these comments:
"The investigation of thyroid dysfunction in horses, as in other species, is fraught with difficulties, because of the multisystemic and non-specific effects of thyroid hormones and because of the currently (commercially) available thyroid function tests, few are specific and many are altered by extrathyroidal factors.
"The type of animals used to establish the normal range for a laboratory test is an often-overlooked, but critically important factor. For example, the use of a reference range derived from normal, adult horse test results for an interpretation of results from a neonatal animal is questionable. This is particularly true when thyroid hormone levels are interpreted in horses, since neonatal foals have much higher T3 and T4 levels than adult horses.
"A number of factors were identified that could have contributed to the low levels of thyroid hormones in these mares and foals (at the two central Kentucky farms), which further substantiates how complex thyroid dysfunction is in horses, and how difficult it is to diagnose. None of the mares or foals were known to be clinically ill or showed any signs associated with thyroid dysfunction. Attempts at treatment appeared to have little, if any, beneficial effect relative to thyroid function and might have contributed to the low thyroid hormone levels."
Messer s final comment in the above statement begs another question. Are many horse owners wasting their money on thyroid hormone supplements?
Messer, who says he doesn t pretend to have all the answers, provides this response to the above question:
"Is it appropriate to supplement thyroid hormones to horses when we don t know whether the thyroid gland is abnormal? I believe that a large percentage of horses that are diagnosed as having hypothyroidism have a normal thyroid gland."
Perhaps when the TSH assay test becomes commercially available, that question will have a definitive answer.
About the Author
Les Sellnow is a free-lance writer based near Riverton, Wyo. He specializes in articles on equine research, and operates a ranch where he raises horses and livestock. He has authored several fiction and non-fiction books, including Understanding Equine Lameness and Understanding The Young Horse, published by Eclipse Press and available at www.exclusivelyequine.com or by calling 800/582-5604.