Thyroid gland in Dog, Cat, Horse and Co, an Interpretation guide
The knowledge of thyroid diseases in dogs and cats is common standard for most small animal vets. However, thyroid disease or defect in the iodine-metabolism by exotics and especially horses are now being diagnosed more frequently as being the underlying cause for different symptom complexes.
Although often part of your routine diagnostics by senior dogs and cats, the lab result interpretations can still be difficult in some cases, and even cause real problems with exotic or equine cases, as they are not yet routine.
Classically, thyroid disease in dogs, cats but also most exotics are clinically seen in middle aged or elderly patients, mostly with a long history of diseases. These histories of diseases make the diagnosis more difficult as the secretion of thyroid hormones can be strongly influenced by other diseases.
A new variant of hyperthyroidism in dogs and cats, which can be found in young animals too, is now seen. The feeding of raw meat, e.g. Barf feeding, sometimes include the feeding of throats. As the removal of thyroid glands is not always considered (even from commercially made diets), and some feeding protocols include daily rations of throats, “hyperthyroidism” with secondary low TSH and consequently thyroid gland atrophy can be the outcome.
It is different within horses, where thyroid problems often are caused by iodine deficiency, which can occur also in young animals, foals or even intrauterine.
Several clues can lead you to the differential diagnose of thyroid disease:
• The clinical symptomatic of hyper- or hypothyroidism.
• A lab result, included in a screening test.
• Testing of a specific breed of dog as part of it receiving its breeding-permit.
If thyroid disease is suspected thyroid hormones are measured to confirm the diagnosis. Which parameter to test first varies from vet to vet, and depends on great extends on the clinical symptoms, the age of animal and secondary disease found.
Is most often the parameter of first choice for diagnosing thyroid disease.
TT4 (=Total T4) is the protein bound T4 and tells you about the circulating reserve pool. The binding to transport proteins makes it possible to distribute the lipophilic and water insoluble thyroxin molecule.
There are species differences: In dogs, cats and rabbits T4 is solely bound by pre-albumin and albumin, whereas in horses and ruminants T4 is also bound to Thyroxin-binding-globulin (TBG).
TBG’s are specific binding globulins that are synthesized in the liver. As for albumin its syntheses and metabolism are influenced by several diseases. Particularly by acute liver disease where the TBG concentration rises due to increased release and decreased clearance. Because of the different, also species specific, half life of the transport proteins the half life of the circulating TT4 and TT3 varies as well. The half life of TT4-Albumin is mentioned as being 16 h and that for the TT4-TGB to be 7 days. The albumin-binding is genetically oldest; the TGB-binding has the advantage of a larger storage capacity, which seems to be of great importance to especially plant eaters. Most meat eaters can on the other hand digest sufficient iodine from their diet.
Result interpretations are tricky when disease is present which influence the protein syntheses and -metabolism. Hypoalbuminemia due to protein loss (enteropathies, nephropathies), diminished syntheses (e.g. by <25 % liver function, inflammation) or redistribution to extra-vascular spaces (vasculitis) as well as hyperalbuminemia (dehydration or Morbus Cushing) can cause measured TT4-values, which do not correlate with the actual thyroid activity. TT4 is somewhat uninfluenced by the sample quality (lipaemia and haemolyse can cause problems with the measurement of the free hormones like fT4.
Different medications can alter the thyroid hormone bindings to the transport proteins and subsequently make the test result questionable e.g. barbiturates, salicylates and penicillin displaces thyroxin from the albumin bindings and the bindings on TBG are competitive inhibited from salicylates, heparin, diazepam, sulfonylurea, phenylbutazone and diphenylhydantoin.
Rabbits and Guinea pigs have, due to an almost non-existent TBG-concentration a very short TT4 and TT3 half time. It has been established that fT4 shows the thyroid function the clearest, especially by hyperthyroidism.
Avians have very low thyroid hormone concentrations, which makes the measurement very difficult as most test systems cannot detect such low concentrations. Also here the measurement of fT4 might be helpful.
TT4 is only slightly influenced by the current metabolism and reflects the thyroid function over time and also the euthyroid sick syndrome the best.
TT4 is very suitable for patients, where no history of altered protein metabolism is present, e.g. dermatology patients where endocrinopathies are suspected, after ruling out Cushing’s disease.
The TSH-concentration is by humans the parameter of first choice. By animals only validated and reliable test systems are available for dogs and cats. For patients with suspected hyperthyroidism – especially for cats - it is the parameter of first choice and can, when corresponding symptomatic is present, substitute the TT4-measurement and when additional changes in the proteins are present secure the diagnose.
The measurement of TSH in serum is often also the parameter of first choice in dogs. Limitations are that with increasing duration of disease, the TSH-concentrations are measures within the normal reference range.
Newer studies have shown that the cTSH-concentrations are within the normal reference range in 13-40% of hypothyroid dogs. Reasons for these low measurements can be exhaustion of the pituitary gland due to long-term hypothyroidism or the proportional increase of TSH-isomers, which cannot be detected by the test system.
Much different than by human diagnostics, only positive results are diagnostic in dogs. A sole measurement of THS is not recommended.
The TSH-concentration is also altered by clinical latent dysfunctions where the measured thyroid hormones are still within the normal reference range, but the secretion from the pituitary gland cannot keep up with the demand. There are only few pathophysiological situations where the increased TSH-concentration does not correlate with the situation of the thyroid. TSH can increase due to a regeneration phase after illness or during pregnancy.
Notice: Numerous drugs are able to inhibit the TSH-secretion from the pituitary gland, like: Glucocorticoids, dopamine-agonists, dopamine,somatostatin. And able to increase the basal and stimulated TSH are metoclopramide and domperidone potent stimulators (strong effect) and chlorpromazine (low effect).
Summary: TSH is by cats your parameter of first choice. By dogs TSH is not suited as a single parameter and only diagnostic when positive. TSH belongs nevertheless to the entry diagnostics and is when it comes to therapy control the parameter of first choice.
Free T4 (fT4)
Free thyroid hormone are only circulating in the blood in very low concentrations (fT4 0.1-0.3% of the TT4). Because of its lipophilic character the blood transportation plays no significant role.
Only un-bound thyroid hormone can escape into the target cells and have a hormonal effect (free-hormone-hypothesis), so the body tries to keep the concentration outside the target cells as long as possible in a sufficient upright concentration adapted to the metabolism needed (e.g. reaction to exposure to cold). FT4 is excreted via bile and partly via the enterohepatic system with species specific different degrees of reabsorption (dog only 20% other species > 80%), so even enteropathies can have a direct impact on the thyroxin household. The absorption into the target cells can also be negatively influenced by NSAID-drugs. If administrated for a long time, both fT4 and T4 will move to the high end of the reference range together with TSH being high, without this being a pituitary or thyroid problem.
Summary: fT4 is not influenced by the protein syntheses and -metabolism and is therefore the parameter of first choice by patients suspicious of euthyroid sick syndrome (patients with other diseases which alter the TT4 and TSH concentrations).
A few remarks regarding measurement:
Different methods are available. For a long time a method with a special sample handling – equilibrium dialyse fT4 (a technique from the 1960´s) – was propagated. This was for a long time the only possibility to determine the extreme low concentrations without TT4 influence.
Due to the highly advanced modern techniques which include highly specific monoclonal antibodies, it is possible to obtain reliably fT4 results, as shown in several new studies, without the complex step of dialyse.
(TgAb; measurement is only possible in dogs)
TgAb is not a first choice parameter to diagnose thyroid gland malfunction, as the concentration does not say anything about the current thyroid function or the prognosis of a hypothyroidism.
The present of TgAb could be the reason for a possible later developing hypothyroidism. TgAb are found by the autoimmune disease of chronic lymphocytic thyreoiditis. In this disease, which can stretch over years, a progressive destruction of the thyroid follicles take place. Clinical symptoms are not seen before only 25% functional tissue is left. By that time the TgAb concentrations are often back to a normal level. In many cases auto-antibodies towards T3 and T4 can be found too.
Summary: The measurement of TgAb concentrations is useful by patients who presents themselves young and by patients where an autoimmune thyreoiditis are suspected (a supposedly genetic component).
The circulating TT3 pool is mainly produced by de-iodination from fT4 in the liver and kidney, and only a small part is secreted directly by the thyroid gland (4:1-ratio by humans). By a decreased thyroid function or an iodine deficit more T3 will be synthesised as compensation and the ratio T4:T3 will change to the favour of T3. If liver- or kidney functions are impaired a short drop in the circulating T3 to T4 can occur. The thyroid gland responds with an increased T3 syntheses and secretion. The same happens with a chronic iodine and selenium deficit. Selenium is an elementary part of the de-iodination in the periphery, and also here the thyroid reacts by reducing the T4 and increasing the T3 syntheses.
The plasma half life of T3 is only 5-6 hours and it only binds to albumin (in humans it binds to both TBG and albumin with a half life of 24-36 hours), which is much shorter as for TT4, and therefore reacts much quicker on changes in protein household as the TT4.
Summary: As the body in critical situations force the syntheses of T3, TT3 cannot be used to diagnose hypothyroidism as a sole parameter. Also the early stages of hyperthyroidism cannot be diagnosed solely by TT3 measurements due to the reduction in the de-iodination.
The measurement of fT3 concentration do not reflect the thyroid function as circulating T3 are only bound to transport proteins in relevant amounts. fT4 are de-ionized as required into fT3 and rfT3 (an inactive iso-form of fT3, which is broken down over several steps. During the de-ionization to rfT3 increased fT4 concentrations are inactivated without impacting the metabolism.
Iodine and Selenium
Iodine and selenium uptake are by carnivores in principle sufficient. By many omnivores and especially herbivores (as equines) does both under- or over-supplementation with these two trace minerals a central role by the thyroid hormone related diseases. Iodine is the building block for thyroid hormones and selenium function in the form of selenocysteine as a central element in the deiodinase. Herbivores work with different mechanisms against the shrinking and most often very low concentration in their natural diet. Mechanisms are e.g. bindings to TBG, profound absorption of the iodine and selenium from the diet intake and re-absorption; the iodine excreted via the bile into the intestines (up to 80 % in herbi- and omnivores). Even with home grown feeding there can be under supplementations in many regions and subsequently alimentary related hypothyroidism. As this is known by most horse owners, and mentioned by the feed industry, over-supplementations like iodine-toxicosis are more likely to occur as the animals do not have mechanism to accelerate their excretion.
Diagnostics using T4 and TSH. By continuing medication or protein disorders additional fT4
Initial diagnostics using T4 + TSH or fT4 + TSH.
Breeding testing dogs:
By familiar history or by certain breeds are TgAb measured
Different function tests are available (see manual)
T4 (or fT4, if fT4 was used for diagnose) + TSH
Medication BID: T4 + TSH 2-4 h p.p.
Medication SID: T4 + TSH 4 h p.p. plus perhaps before medication
True hyper- or hypothyroidisms are rare. The supplementation of iodine, selenium and zinc should be checked from a serum sample.
Hypo and hyperthyroidism are described. As diagnostics are TT4 used to diagnose hypothyroidism and fT4 for hyperthyroidism.